Janssen Announces U.S. FDA Approval of CABENUVA (rilpivirine and cabotegravir), the First Long-Acting Regimen for the Treatment of HIV
TITUSVILLE, N.J., January 21, 2021 – The Janssen Pharmaceutical Companies of Johnson & Johnson today announced the U.S. Food and Drug Administration (FDA) has approved CABENUVA (consisting of Janssen’s rilpivirine and ViiV Healthcare’s cabotegravir), the first and only once-monthly, long-acting regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults. The novel regimen was co-developed as part of a collaboration with ViiV Healthcare and builds on Janssen’s 25-year commitment to make HIV history. In the U.S., ViiV Healthcare is the marketing authorization holde...
Source: Johnson and Johnson - January 22, 2021 Category: Pharmaceuticals Tags: Innovation Source Type: news

Separation anxiety
(Source: ScienceNOW)
Source: ScienceNOW - January 21, 2021 Category: Science Authors: Leslie, M. Tags: Biochemistry, Cell Biology Feature Source Type: news

Cross-talk between histone modifications
(Source: ScienceNOW)
Source: ScienceNOW - January 21, 2021 Category: Science Authors: Purnell, B. A. Tags: Biochemistry twis Source Type: news

Cryo-EM uncovers polycomb interactions
(Source: ScienceNOW)
Source: ScienceNOW - January 21, 2021 Category: Science Authors: Purnell, B. A. Tags: Biochemistry twis Source Type: news

JARID2 and AEBP2 regulate PRC2 in the presence of H2AK119ub1 and other histone modifications
Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) cooperate to determine cell identity by epigenetic gene expression regulation. However, the mechanism of PRC2 recruitment by means of recognition of PRC1-mediated H2AK119ub1 remains poorly understood. Our PRC2 cryo–electron microscopy structure with cofactors JARID2 and AEBP2 bound to a H2AK119ub1-containing nucleosome reveals a bridge helix in EZH2 that connects the SET domain, H3 tail, and nucleosomal DNA. JARID2 and AEBP2 each interact with one ubiquitin and the H2A-H2B surface. JARID2 stimulates PRC2 through interactions with both the polycomb protein EED and ...
Source: ScienceNOW - January 21, 2021 Category: Science Authors: Kasinath, V., Beck, C., Sauer, P., Poepsel, S., Kosmatka, J., Faini, M., Toso, D., Aebersold, R., Nogales, E. Tags: Biochemistry, Online Only r-articles Source Type: news

Regulation of the Dot1 histone H3K79 methyltransferase by histone H4K16 acetylation
Dot1 (disruptor of telomeric silencing-1), the histone H3 lysine 79 (H3K79) methyltransferase, is conserved throughout evolution, and its deregulation is found in human leukemias. Here, we provide evidence that acetylation of histone H4 allosterically stimulates yeast Dot1 in a manner distinct from but coordinating with histone H2B ubiquitination (H2BUb). We further demonstrate that this stimulatory effect is specific to acetylation of lysine 16 (H4K16ac), a modification central to chromatin structure. We provide a mechanism of this histone cross-talk and show that H4K16ac and H2BUb play crucial roles in H3K79 di- and trim...
Source: ScienceNOW - January 21, 2021 Category: Science Authors: Valencia-Sanchez, M. I., De Ioannes, P., Wang, M., Truong, D. M., Lee, R., Armache, J.-P., Boeke, J. D., Armache, K.-J. Tags: Biochemistry, Online Only r-articles Source Type: news

Model for rare cancer results instead in obesity
While a typo in a letter or email is a problem it's not a big one, usually. But when that typo is in genetic code, it's a very different matter. Mayo researchers in the lab of L. James Maher, III, Ph.D., a Mayo Clinic biochemist, and their collaborators, are examining a genetic typo that can lead [...] (Source: News from Mayo Clinic)
Source: News from Mayo Clinic - January 19, 2021 Category: Databases & Libraries Source Type: news

Royal Society award enables University researcher to study neurodegenerative disease
Professor Peter Cullen, a Wellcome Trust Investigator from the School of Biochemistry at the University of Bristol, has been awarded the Royal Society Noreen Murray Professorship to expand his research into neurological sciences. (Source: University of Bristol news)
Source: University of Bristol news - January 15, 2021 Category: Universities & Medical Training Tags: Announcements, Staff notices; Faculty of Biomedical Sciences, School of Biochemistry, Faculty of Biomedical Sciences Source Type: news

LSU Health awarded $2.5m grant to reduce stroke risk for obese women on contraceptives
(Louisiana State University Health Sciences Center) The National Heart, Lung, and Blood Institute of the National Institutes of Health has awarded Rinku Majumder, PhD, Associate Professor of Biochemistry& Molecular Biology at LSU Health New Orleans School of Medicine, a $2.5 million grant over four years to help reduce the high stroke risk to women with obesity who take estrogen-containing birth control pills. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - January 14, 2021 Category: International Medicine & Public Health Source Type: news

A key complex in B cell activation
(Source: ScienceNOW)
Source: ScienceNOW - January 14, 2021 Category: Science Authors: Vinson, V. Tags: Biochemistry, Cell Biology twis Source Type: news

A tight couple makes messenger RNAs
(Source: ScienceNOW)
Source: ScienceNOW - January 14, 2021 Category: Science Authors: Jiang, D. Tags: Biochemistry, Molecular Biology twis Source Type: news

Structure of a transcribing RNA polymerase II-U1 snRNP complex
To initiate cotranscriptional splicing, RNA polymerase II (Pol II) recruits the U1 small nuclear ribonucleoprotein particle (U1 snRNP) to nascent precursor messenger RNA (pre-mRNA). Here, we report the cryo–electron microscopy structure of a mammalian transcribing Pol II–U1 snRNP complex. The structure reveals that Pol II and U1 snRNP interact directly. This interaction positions the pre-mRNA 5' splice site near the RNA exit site of Pol II. Extension of pre-mRNA retains the 5' splice site, leading to the formation of a "growing intron loop." Loop formation may facilitate scanning of nascent pre-mRNA f...
Source: ScienceNOW - January 14, 2021 Category: Science Authors: Zhang, S., Aibara, S., Vos, S. M., Agafonov, D. E., Lührmann, R., Cramer, P. Tags: Biochemistry, Molecular Biology reports Source Type: news

Cryo-EM structure of the B cell co-receptor CD19 bound to the tetraspanin CD81
Signaling through the CD19-CD81 co-receptor complex, in combination with the B cell receptor, is a critical determinant of B cell development and activation. It is unknown how CD81 engages CD19 to enable co-receptor function. Here, we report a 3.8-angstrom structure of the CD19-CD81 complex bound to a therapeutic antigen-binding fragment, determined by cryo–electron microscopy (cryo-EM). The structure includes both the extracellular domains and the transmembrane helices of the complex, revealing a contact interface between the ectodomains that drives complex formation. Upon binding to CD19, CD81 opens its ectodomain ...
Source: ScienceNOW - January 14, 2021 Category: Science Authors: Susa, K. J., Rawson, S., Kruse, A. C., Blacklow, S. C. Tags: Biochemistry, Cell Biology reports Source Type: news

UT Southwestern biochemist recognized for pioneering metabolic research
(TAMEST) DALLAS - UT Southwestern Biochemist Benjamin Tu, Ph.D., is the recipient of the 2021 Edith and Peter O'Donnell Award in Science from TAMEST (The Academy of Medicine, Engineering and Science of Texas). He was chosen for his pioneering research on cellular roles of small molecule metabolites that may have relevance for cancer treatments and other diseases. (Source: EurekAlert! - Cancer)
Source: EurekAlert! - Cancer - January 13, 2021 Category: Cancer & Oncology Source Type: news

mRNA Technology Gave Us the First COVID-19 Vaccines. It Could Also Upend the Drug Industry
“No!” The doctor snapped. “Look at me!” I had been staring her in the eyes, as she had ordered, but when a doctor on my other side began jabbing me with a needle, I started to turn my head. “Don’t look at it,” the first doctor said. I obeyed. This was in early August in New Orleans, where I had signed up to be a participant in the clinical trial for the Pfizer-BioNTech COVID-19 vaccine. It was a blind study, which meant I was not supposed to know whether I had gotten the placebo or the real vaccine. I asked the doctor if I would really been able to tell by looking at the syringe. &...
Source: TIME: Science - January 11, 2021 Category: Science Authors: Walter Isaacson Tags: Uncategorized COVID-19 feature Magazine Source Type: news

mRNA Technology Gave Us the First COVID-19 Vaccines. It Could Also Upend the Drug Industry
“No!” The doctor snapped. “Look at me!” I had been staring her in the eyes, as she had ordered, but when a doctor on my other side began jabbing me with a needle, I started to turn my head. “Don’t look at it,” the first doctor said. I obeyed. This was in early August in New Orleans, where I had signed up to be a participant in the clinical trial for the Pfizer-BioNTech COVID-19 vaccine. It was a blind study, which meant I was not supposed to know whether I had gotten the placebo or the real vaccine. I asked the doctor if I would really been able to tell by looking at the syringe. &...
Source: TIME: Health - January 11, 2021 Category: Consumer Health News Authors: Walter Isaacson Tags: Uncategorized COVID-19 feature Magazine Source Type: news

Mechanism of spliceosome remodeling by the ATPase/helicase Prp2 and its coactivator Spp2
Spliceosome remodeling, executed by conserved adenosine triphosphatase (ATPase)/helicases including Prp2, enables precursor messenger RNA (pre-mRNA) splicing. However, the structural basis for the function of the ATPase/helicases remains poorly understood. Here, we report atomic structures of Prp2 in isolation, Prp2 complexed with its coactivator Spp2, and Prp2-loaded activated spliceosome and the results of structure-guided biochemical analysis. Prp2 weakly associates with the spliceosome and cannot function without Spp2, which stably associates with Prp2 and anchors on the spliceosome, thus tethering Prp2 to the activate...
Source: ScienceNOW - January 7, 2021 Category: Science Authors: Bai, R., Wan, R., Yan, C., Jia, Q., Lei, J., Shi, Y. Tags: Biochemistry, Online Only r-articles Source Type: news

Tubulin glycylation controls axonemal dynein activity, flagellar beat, and male fertility
In this study, we generated a mouse model entirely lacking tubulin glycylation. Male mice were subfertile owing to aberrant beat patterns of their sperm flagella, which impeded the straight swimming of sperm cells. Using cryo–electron tomography, we showed that lack of glycylation caused abnormal conformations of the dynein arms within sperm axonemes, providing the structural basis for the observed dysfunction. Our findings reveal the importance of microtubule glycylation for controlled flagellar beating, directional sperm swimming, and male fertility. (Source: ScienceNOW)
Source: ScienceNOW - January 7, 2021 Category: Science Authors: Gadadhar, S., Alvarez Viar, G., Hansen, J. N., Gong, A., Kostarev, A., Ialy-Radio, C., Leboucher, S., Whitfield, M., Ziyyat, A., Toure, A., Alvarez, L., Pigino, G., Janke, C. Tags: Biochemistry, Cell Biology, Online Only r-articles Source Type: news

Structural basis for antibody inhibition of flavivirus NS1-triggered endothelial dysfunction
Medically important flaviviruses cause diverse disease pathologies and collectively are responsible for a major global disease burden. A contributing factor to pathogenesis is secreted flavivirus nonstructural protein 1 (NS1). Despite demonstrated protection by NS1-specific antibodies against lethal flavivirus challenge, the structural and mechanistic basis remains unknown. Here, we present three crystal structures of full-length dengue virus NS1 complexed with a flavivirus–cross-reactive, NS1-specific monoclonal antibody, 2B7, at resolutions between 2.89 and 3.96 angstroms. These structures reveal a protective mecha...
Source: ScienceNOW - January 7, 2021 Category: Science Authors: Biering, S. B., Akey, D. L., Wong, M. P., Brown, W. C., Lo, N. T. N., Puerta-Guardo, H., Tramontini Gomes de Sousa, F., Wang, C., Konwerski, J. R., Espinosa, D. A., Bockhaus, N. J., Glasner, D. R., Li, J., Blanc, S. F., Juan, E. Y., Elledge, S. J., Mina, Tags: Biochemistry, Microbiology reports Source Type: news

A broadly protective antibody that targets the flavivirus NS1 protein
There are no approved flaviviral therapies and the development of vaccines against flaviruses has the potential of being undermined by antibody-dependent enhancement (ADE). The flavivirus nonstructural protein 1 (NS1) is a promising vaccine antigen with low ADE risk but has yet to be explored as a broad-spectrum therapeutic antibody target. Here, we provide the structural basis of NS1 antibody cross-reactivity through cocrystallization of the antibody 1G5.3 with NS1 proteins from dengue and Zika viruses. The 1G5.3 antibody blocks multi-flavivirus NS1-mediated cell permeability in disease-relevant cell lines, and therapeuti...
Source: ScienceNOW - January 7, 2021 Category: Science Authors: Modhiran, N., Song, H., Liu, L., Bletchly, C., Brillault, L., Amarilla, A. A., Xu, X., Qi, J., Chai, Y., Cheung, S. T. M., Traves, R., Setoh, Y. X., Bibby, S., Scott, C. A. P., Freney, M. E., Newton, N. D., Khromykh, A. A., Chappell, K. J., Muller, D. A., Tags: Biochemistry, Microbiology reports Source Type: news

Pre-T cell receptors topologically sample self-ligands during thymocyte {beta}-selection
Self-discrimination, a critical but ill-defined molecular process programmed during thymocyte development, requires myriad pre–T cell receptors (preTCRs) and αβTCRs. Using x-ray crystallography, we show how a preTCR applies the concave β-sheet surface of its single variable domain (Vβ) to "horizontally" grab the protruding MHC α2-helix. By contrast, αβTCRs purpose all six complementarity-determining region (CDR) loops of their paired VαVβ module to recognize peptides bound to major histocompatibility complex molecules (pMHCs) in "vertical" head-to-h...
Source: ScienceNOW - January 7, 2021 Category: Science Authors: Li, X., Mizsei, R., Tan, K., Mallis, R. J., Duke-Cohan, J. S., Akitsu, A., Tetteh, P. W., Dubey, A., Hwang, W., Wagner, G., Lang, M. J., Arthanari, H., Wang, J.-h., Reinherz, E. L. Tags: Biochemistry, Immunology reports Source Type: news

PreTCRs use horizontal docking geometry
(Source: ScienceNOW)
Source: ScienceNOW - January 7, 2021 Category: Science Authors: Scanlon, S. T. Tags: Biochemistry, Immunology twis Source Type: news

Glycylation regulates axonemal dyneins
(Source: ScienceNOW)
Source: ScienceNOW - January 7, 2021 Category: Science Authors: Hurtley, S. M. Tags: Biochemistry, Cell Biology twis Source Type: news

Remodeling an RNA processing machine
(Source: ScienceNOW)
Source: ScienceNOW - January 7, 2021 Category: Science Authors: Jiang, D. Tags: Biochemistry twis Source Type: news

Two antibodies against flaviviruses
(Source: ScienceNOW)
Source: ScienceNOW - January 7, 2021 Category: Science Authors: Vinson, V. Tags: Biochemistry, Microbiology twis Source Type: news

Epigenetic enzymes and regulation of transcription
NIEHS biochemist Trevor Archer, Ph.D., discussed “Using Epigenetic Enzymes to Regulate Transcription,” in a Duke University seminar. (read more) (Source: Environmental Factor - NIEHS Newsletter)
Source: Environmental Factor - NIEHS Newsletter - January 6, 2021 Category: Environmental Health Source Type: news

Structural basis of antagonizing the vitamin K catalytic cycle for anticoagulation
Vitamin K antagonists are widely used anticoagulants that target vitamin K epoxide reductases (VKOR), a family of integral membrane enzymes. To elucidate their catalytic cycle and inhibitory mechanism, we report 11 x-ray crystal structures of human VKOR and pufferfish VKOR-like, with substrates and antagonists in different redox states. Substrates entering the active site in a partially oxidized state form cysteine adducts that induce an open-to-closed conformational change, triggering reduction. Binding and catalysis are facilitated by hydrogen-bonding interactions in a hydrophobic pocket. The antagonists bind specificall...
Source: ScienceNOW - December 31, 2020 Category: Science Authors: Liu, S., Li, S., Shen, G., Sukumar, N., Krezel, A. M., Li, W. Tags: Biochemistry, Online Only r-articles Source Type: news

Steps toward translocation-independent RNA polymerase inactivation by terminator ATPase {rho}
Factor-dependent transcription termination mechanisms are poorly understood. We determined a series of cryo–electron microscopy structures portraying the hexameric adenosine triphosphatase (ATPase) on a pathway to terminating NusA/NusG-modified elongation complexes. An open ring contacts NusA, NusG, and multiple regions of RNA polymerase, trapping and locally unwinding proximal upstream DNA. NusA wedges into the ring, initially sequestering RNA. Upon deflection of distal upstream DNA over the RNA polymerase zinc-binding domain, NusA rotates underneath one capping subunit, which subsequently captures RNA. After detach...
Source: ScienceNOW - December 31, 2020 Category: Science Authors: Said, N., Hilal, T., Sunday, N. D., Khatri, A., Bürger, J., Mielke, T., Belogurov, G. A., Loll, B., Sen, R., Artsimovitch, I., Wahl, M. C. Tags: Biochemistry, Online Only r-articles Source Type: news

Evolution of fold switching in a metamorphic protein
Metamorphic proteins switch between different folds, defying the protein folding paradigm. It is unclear how fold switching arises during evolution. With ancestral reconstruction and nuclear magnetic resonance, we studied the evolution of the metamorphic human protein XCL1, which has two distinct folds with different functions, making it an unusual member of the chemokine family, whose members generally adopt one conserved fold. XCL1 evolved from an ancestor with the chemokine fold. Evolution of a dimer interface, changes in structural constraints and molecular strain, and alteration of intramolecular protein contacts drov...
Source: ScienceNOW - December 31, 2020 Category: Science Authors: Dishman, A. F., Tyler, R. C., Fox, J. C., Kleist, A. B., Prehoda, K. E., Babu, M. M., Peterson, F. C., Volkman, B. F. Tags: Biochemistry reports Source Type: news

CDC20 assists its catalytic incorporation in the mitotic checkpoint complex
Open (O) and closed (C) topologies of HORMA-domain proteins are respectively associated with inactive and active states of fundamental cellular pathways. The HORMA protein O-MAD2 converts to C-MAD2 upon binding CDC20. This is rate limiting for assembly of the mitotic checkpoint complex (MCC), the effector of a checkpoint required for mitotic fidelity. A catalyst assembled at kinetochores accelerates MAD2:CDC20 association through a poorly understood mechanism. Using a reconstituted SAC system, we discovered that CDC20 is an impervious substrate for which access to MAD2 requires simultaneous docking on several sites of the ...
Source: ScienceNOW - December 31, 2020 Category: Science Authors: Piano, V., Alex, A., Stege, P., Maffini, S., Stoppiello, G. A., Huis in t Veld, P. J., Vetter, I. R., Musacchio, A. Tags: Biochemistry, Cell Biology reports Source Type: news

A tripartite mechanism catalyzes Mad2-Cdc20 assembly at unattached kinetochores
During cell division, kinetochores couple chromosomes to spindle microtubules. To protect against chromosome gain or loss, kinetochores lacking microtubule attachment locally catalyze association of the checkpoint proteins Cdc20 and Mad2, which is the key event in the formation of a diffusible checkpoint complex that prevents mitotic exit. We elucidated the mechanism of kinetochore-catalyzed Mad2-Cdc20 assembly with a probe that specifically monitors this assembly reaction at kinetochores in living cells. We found that catalysis occurs through a tripartite mechanism that includes localized delivery of Mad2 and Cdc20 substr...
Source: ScienceNOW - December 31, 2020 Category: Science Authors: Lara-Gonzalez, P., Kim, T., Oegema, K., Corbett, K., Desai, A. Tags: Biochemistry, Cell Biology reports Source Type: news

How to stop RNA polymerase
(Source: ScienceNOW)
Source: ScienceNOW - December 31, 2020 Category: Science Authors: Jiang, D. Tags: Biochemistry twis Source Type: news

Anticoagulants take over
(Source: ScienceNOW)
Source: ScienceNOW - December 31, 2020 Category: Science Authors: Funk, M. A. Tags: Biochemistry twis Source Type: news

One sequence encoding two structures
(Source: ScienceNOW)
Source: ScienceNOW - December 31, 2020 Category: Science Authors: Vinson, V. Tags: Biochemistry twis Source Type: news

Checking fidelity in cell division
(Source: ScienceNOW)
Source: ScienceNOW - December 31, 2020 Category: Science Authors: Ray, L. B. Tags: Biochemistry, Cell Biology twis Source Type: news

Protein twist and squeeze confers cancer drug resistance
(Kyoto University) In 1986, cellular biochemist Kazumitsu Ueda, currently at Kyoto University's Institute for Integrated Cell-Material Sciences (iCeMS), discovered that a protein called ABCB1 could transport multiple chemotherapeutics out of some cancer cells, making them resistant to treatment. How it did this has remained a mystery for the past 35 years. Now, his team has published a review in the journalFEBS Letters, summarizing what they have learned following years of research on this and other ATP-binding cassette (ABC) transporter proteins. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - December 29, 2020 Category: Biology Source Type: news

Switching DNA functions on and off by means of light
(University of M ü nster) Biochemists at M ü nster University have developed a new strategy for controlling the biological functions of DNA (deoxyribonucleic acid) by means of light and therefore provide a tool to investigate processes which take place in cells. The results have been published in the journalAngewandte Chemie. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - December 28, 2020 Category: Biology Source Type: news

Groundwork for COVID-19 Vaccine Laid at Dartmouth
Discoveries originating in a basic science lab at the Geisel School of Medicine are being used in the newly approved COVID-19 vaccine from the Pfizer/BioNTech partnership. (Source: News at Dartmouth Medical School)
Source: News at Dartmouth Medical School - December 17, 2020 Category: Hospital Management Authors: Timothy Dean Tags: News Press Release Research biochemistry cell biology COVID-19 vaccine Source Type: news

Researcher boosts vegetable oil production in plant leaves
(University of Missouri-Columbia) Jay Thelen, a professor of biochemistry at the University of Missouri, has found a way to boost the production of triacylglycerol -- the main component of vegetable oil -- in plant leaves, a technique that could allow producers to harvest oil from large, leafy plants that also have other uses. Sorghum, for example -- a global source of grain prized for its drought-resistant qualities -- could serve a dual role as a source of vegetable oil, creating a more efficient and valuable crop. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - December 17, 2020 Category: Biology Source Type: news

Mechanism of protein-guided folding of the active site U2/U6 RNA during spliceosome activation
Spliceosome activation involves extensive protein and RNA rearrangements that lead to formation of a catalytically active U2/U6 RNA structure. At present, little is known about the assembly pathway of the latter and the mechanism whereby proteins aid its proper folding. Here, we report the cryo–electron microscopy structures of two human, activated spliceosome precursors (that is, pre-Bact complexes) at core resolutions of 3.9 and 4.2 angstroms. These structures elucidate the order of the numerous protein exchanges that occur during activation, the mutually exclusive interactions that ensure the correct order of ribo...
Source: ScienceNOW - December 17, 2020 Category: Science Authors: Townsend, C., Leelaram, M. N., Agafonov, D. E., Dybkov, O., Will, C. L., Bertram, K., Urlaub, H., Kastner, B., Stark, H., Lührmann, R. Tags: Biochemistry, Molecular Biology, Online Only r-articles Source Type: news

Versatile and multivalent nanobodies efficiently neutralize SARS-CoV-2
In this study, we used camelid immunization and proteomics to identify a large repertoire of highly potent neutralizing nanobodies (Nbs) to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein receptor binding domain (RBD). We discovered Nbs with picomolar to femtomolar affinities that inhibit viral infection at concentrations below the nanograms-per-milliliter level, and we determined a structure of one of the most potent Nbs in complex with the RBD. Structural proteomics and integrative modeling revealed multiple distinct and nonoverlapping epitopes and indicated an array of potential neutraliza...
Source: ScienceNOW - December 17, 2020 Category: Science Authors: Xiang, Y., Nambulli, S., Xiao, Z., Liu, H., Sang, Z., Duprex, W. P., Schneidman-Duhovny, D., Zhang, C., Shi, Y. Tags: Biochemistry, Immunology reports Source Type: news

An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells via an interaction between its Spike protein and the host cell receptor angiotensin-converting enzyme 2 (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt the interaction between Spike and ACE2. Cryo–electron microscopy (cryo-EM) revealed that one nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains locked into their inaccessible down state, incapable of binding ACE2. Affinity maturation and structure-guided design o...
Source: ScienceNOW - December 17, 2020 Category: Science Authors: Schoof, M., Faust, B., Saunders, R. A., Sangwan, S., Rezelj, V., Hoppe, N., Boone, M., Billesbolle, C. B., Puchades, C., Azumaya, C. M., Kratochvil, H. T., Zimanyi, M., Deshpande, I., Liang, J., Dickinson, S., Nguyen, H. C., Chio, C. M., Merz, G. E., Thom Tags: Biochemistry, Microbiology reports Source Type: news

Two steps forward--now look back
(Source: ScienceNOW)
Source: ScienceNOW - December 17, 2020 Category: Science Authors: Funk, M. A. Tags: Biochemistry twis Source Type: news

Nanobodies that neutralize
(Source: ScienceNOW)
Source: ScienceNOW - December 17, 2020 Category: Science Authors: Vinson, V. Tags: Biochemistry, Immunology twis Source Type: news

Splicing machine shifts into gear
(Source: ScienceNOW)
Source: ScienceNOW - December 17, 2020 Category: Science Authors: Jiang, D. Tags: Biochemistry, Molecular Biology twis Source Type: news

How directed evolution reshapes the energy landscape in an enzyme to boost catalysis
The advent of biocatalysts designed computationally and optimized by laboratory evolution provides an opportunity to explore molecular strategies for augmenting catalytic function. Applying a suite of nuclear magnetic resonance, crystallography, and stopped-flow techniques to an enzyme designed for an elementary proton transfer reaction, we show how directed evolution gradually altered the conformational ensemble of the protein scaffold to populate a narrow, highly active conformational ensemble and accelerate this transformation by nearly nine orders of magnitude. Mutations acquired during optimization enabled global conf...
Source: ScienceNOW - December 17, 2020 Category: Science Authors: Otten, R., Padua, R. A. P., Bunzel, H. A., Nguyen, V., Pitsawong, W., Patterson, M., Sui, S., Perry, S. L., Cohen, A. E., Hilvert, D., Kern, D. Tags: Biochemistry reports Source Type: news

Celia Milstein obituary
My friend Celia Milstein, who has died aged 92, was among those who contributed to the invention of monoclonal antibodies, which led to the Nobel prize for medicine of 1984, won by her husband,C ésar Milstein, with Georges Kohler and Niels Jerne. Monoclonal antibodies are used in both treatment and diagnosis of diseases, including cancers, and are being trialled against Covid-19.Celia was born and grew up in the outskirts of Buenos Aires, to Efrain Prilleltensky, an accountant, and his wife, Ana (nee Davidson), both immigrants from the Ukraine who spoke Yiddish. She recalled her childhood as full of beauty.Continue ...
Source: Guardian Unlimited Science - December 16, 2020 Category: Science Authors: Peter Lawrence Tags: Immunology Medicine Biochemistry and molecular biology Education Medical research Science Source Type: news

Biochemist Josh Sakon chosen as National Academy of Inventors Fellow
(University of Arkansas) Chemistry professor and BiologicsMD co-founder Josh Sakon has been selected as a 2020 National Academy of Inventors fellow. Sakon's inventions address osteoporosis, bone metastasis and alopecia. (Source: EurekAlert! - Cancer)
Source: EurekAlert! - Cancer - December 15, 2020 Category: Cancer & Oncology Source Type: news

Genetic interaction mapping informs integrative structure determination of protein complexes
Determining structures of protein complexes is crucial for understanding cellular functions. Here, we describe an integrative structure determination approach that relies on in vivo measurements of genetic interactions. We construct phenotypic profiles for point mutations crossed against gene deletions or exposed to environmental perturbations, followed by converting similarities between two profiles into an upper bound on the distance between the mutated residues. We determine the structure of the yeast histone H3-H4 complex based on ~500,000 genetic interactions of 350 mutants. We then apply the method to subunits Rpb1-R...
Source: ScienceNOW - December 10, 2020 Category: Science Authors: Braberg, H., Echeverria, I., Bohn, S., Cimermancic, P., Shiver, A., Alexander, R., Xu, J., Shales, M., Dronamraju, R., Jiang, S., Dwivedi, G., Bogdanoff, D., Chaung, K. K., Hüttenhain, R., Wang, S., Mavor, D., Pellarin, R., Schneidman, D., Bader, Tags: Biochemistry, Engineering, Online Only r-articles Source Type: news

Protein condensates as aging Maxwell fluids
Protein condensates are complex fluids that can change their material properties with time. However, an appropriate rheological description of these fluids remains missing. We characterize the time-dependent material properties of in vitro protein condensates using laser tweezer–based active and microbead-based passive rheology. For different proteins, the condensates behave at all ages as viscoelastic Maxwell fluids. Their viscosity strongly increases with age while their elastic modulus varies weakly. No significant differences in structure were seen by electron microscopy at early and late ages. We conclude that p...
Source: ScienceNOW - December 10, 2020 Category: Science Authors: Jawerth, L., Fischer-Friedrich, E., Saha, S., Wang, J., Franzmann, T., Zhang, X., Sachweh, J., Ruer, M., Ijavi, M., Saha, S., Mahamid, J., Hyman, A. A., Jülicher, F. Tags: Biochemistry reports Source Type: news