Robert Simoni, Cellular Membrane Biochemist, Dies at 81
Simoni spent more than four decades at Stanford University as a teacher, researcher, and administrator in the university's biology department. (Source: The Scientist)
Source: The Scientist - September 25, 2020 Category: Science Tags: News & Opinion Source Type: news

The endoplasmic reticulum P5A-ATPase is a transmembrane helix dislocase
Organelle identity depends on protein composition. How mistargeted proteins are selectively recognized and removed from organelles is incompletely understood. Here, we found that the orphan P5A–adenosine triphosphatase (ATPase) transporter ATP13A1 (Spf1 in yeast) directly interacted with the transmembrane segment (TM) of mitochondrial tail–anchored proteins. P5A-ATPase activity mediated the extraction of mistargeted proteins from the endoplasmic reticulum (ER). Cryo–electron microscopy structures of Saccharomyces cerevisiae Spf1 revealed a large, membrane-accessible substrate-binding pocket that alternate...
Source: ScienceNOW - September 24, 2020 Category: Science Authors: McKenna, M. J., Sim, S. I., Ordureau, A., Wei, L., Harper, J. W., Shao, S., Park, E. Tags: Biochemistry, Cell Biology, Online Only r-articles Source Type: news

Designed protein logic to target cells with precise combinations of surface antigens
In this study, we design colocalization-dependent protein switches (Co-LOCKR) that perform AND, OR, and NOT Boolean logic operations. These switches activate through a conformational change only when all conditions are met, generating rapid, transcription-independent responses at single-cell resolution within complex cell populations. We implement AND gates to redirect T cell specificity against tumor cells expressing two surface antigens while avoiding off-target recognition of single-antigen cells, and three-input switches that add NOT or OR logic to avoid or include cells expressing a third antigen. Thus, de novo design...
Source: ScienceNOW - September 24, 2020 Category: Science Authors: Lajoie, M. J., Boyken, S. E., Salter, A. I., Bruffey, J., Rajan, A., Langan, R. A., Olshefsky, A., Muhunthan, V., Bick, M. J., Gewe, M., Quijano-Rubio, A., Johnson, J., Lenz, G., Nguyen, A., Pun, S., Correnti, C. E., Riddell, S. R., Baker, D. Tags: Biochemistry, Molecular Biology reports Source Type: news

Succination inactivates gasdermin D and blocks pyroptosis
Activated macrophages undergo a metabolic switch to aerobic glycolysis, accumulating Krebs’ cycle intermediates that alter transcription of immune response genes. We extended these observations by defining fumarate as an inhibitor of pyroptotic cell death. We found that dimethyl fumarate (DMF) delivered to cells or endogenous fumarate reacts with gasdermin D (GSDMD) at critical cysteine residues to form S-(2-succinyl)-cysteine. GSDMD succination prevents its interaction with caspases, limiting its processing, oligomerization, and capacity to induce cell death. In mice, the administration of DMF protects against lipop...
Source: ScienceNOW - September 24, 2020 Category: Science Authors: Humphries, F., Shmuel-Galia, L., Ketelut-Carneiro, N., Li, S., Wang, B., Nemmara, V. V., Wilson, R., Jiang, Z., Khalighinejad, F., Muneeruddin, K., Shaffer, S. A., Dutta, R., Ionete, C., Pesiridis, S., Yang, S., Thompson, P. R., Fitzgerald, K. A. Tags: Biochemistry, Immunology reports Source Type: news

Distinct conformational states of SARS-CoV-2 spike protein
Intervention strategies are urgently needed to control the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The trimeric viral spike (S) protein catalyzes fusion between viral and target cell membranes to initiate infection. Here, we report two cryo–electron microscopy structures derived from a preparation of the full-length S protein, representing its prefusion (2.9-angstrom resolution) and postfusion (3.0-angstrom resolution) conformations, respectively. The spontaneous transition to the postfusion state is independent of target cells. The prefusion trimer has three receptor-binding domains cl...
Source: ScienceNOW - September 24, 2020 Category: Science Authors: Cai, Y., Zhang, J., Xiao, T., Peng, H., Sterling, S. M., Walsh, R. M., Rawson, S., Rits-Volloch, S., Chen, B. Tags: Biochemistry, Microbiology r-articles Source Type: news

Fumarate targets pyroptosis
(Source: ScienceNOW)
Source: ScienceNOW - September 24, 2020 Category: Science Authors: Scanlon, S. T. Tags: Biochemistry, Immunology twis Source Type: news

Dissecting membrane dislocation
(Source: ScienceNOW)
Source: ScienceNOW - September 24, 2020 Category: Science Authors: Hurtley, S. M. Tags: Biochemistry, Cell Biology twis Source Type: news

A dynamic viral spike
(Source: ScienceNOW)
Source: ScienceNOW - September 24, 2020 Category: Science Authors: Vinson, V. Tags: Biochemistry, Microbiology twis Source Type: news

Logic at the cell surface
(Source: ScienceNOW)
Source: ScienceNOW - September 24, 2020 Category: Science Authors: Vinson, V. Tags: Biochemistry, Molecular Biology twis Source Type: news

Discovery of a druggable pocket in the SARS-CoV-2 Spike protein could stop virus in its tracks
A druggable pocket in the SARS-CoV-2 Spike protein that could be used to stop the virus from infecting human cells has been discovered by an international team of scientists led by the University of Bristol. The researchers say their findings, published today [21 September] in the journal Science, are a potential 'game changer' in defeating the current pandemic and add that small molecule anti-viral drugs developed to target the pocket they discovered could help eliminate COVID-19. (Source: University of Bristol news)
Source: University of Bristol news - September 21, 2020 Category: Universities & Medical Training Tags: Health, International, Research; Faculty of Science, Faculty of Science, School of Chemistry, Institutes, Bristol BioDesign Institute, Institutes, Elizabeth Blackwell, Faculty of Life Sciences, Faculty of Life Sciences, School of Biochemistry, Faculty of Source Type: news

Leslie Iversen obituary
Neuropharmacologist who searched for new gateways for drugs to treat the brain and mindAfflictions of the mind and brain, from stroke to schizophrenia, remain among the most challenging to treat, even after more than half a century of discoveries about the brain ’s biochemistry and how it responds to drugs. The neuropharmacologist Leslie Iversen, who has died aged 82, devoted his career to making sense of the interplay of signalling molecules in the nervous system that might provide sites where drugs could act.After directing laboratories in both the public sector and the pharmaceutical industry, in his later years I...
Source: Guardian Unlimited Science - September 18, 2020 Category: Science Authors: Georgina Ferry Tags: Drugs Science People in science Drugs policy Medicine Source Type: news

How ribosomes are made
(Source: ScienceNOW)
Source: ScienceNOW - September 17, 2020 Category: Science Authors: Vinson, V. Tags: Biochemistry twis Source Type: news

A steric block to SARS-CoV-2
(Source: ScienceNOW)
Source: ScienceNOW - September 17, 2020 Category: Science Authors: Vinson, V. Tags: Biochemistry, Microbiology twis Source Type: news

Stabilizing the prefusion SARS-CoV-2 spike
(Source: ScienceNOW)
Source: ScienceNOW - September 17, 2020 Category: Science Authors: Vinson, V. Tags: Biochemistry, Virology twis Source Type: news

90S pre-ribosome transformation into the primordial 40S subunit
Production of small ribosomal subunits initially requires the formation of a 90S precursor followed by an enigmatic process of restructuring into the primordial pre-40S subunit. We elucidate this process by biochemical and cryo–electron microscopy analysis of intermediates along this pathway in yeast. First, the remodeling RNA helicase Dhr1 engages the 90S pre-ribosome, followed by Utp24 endonuclease–driven RNA cleavage at site A1, thereby separating the 5'-external transcribed spacer (ETS) from 18S ribosomal RNA. Next, the 5'-ETS and 90S assembly factors become dislodged, but this occurs sequentially, not en b...
Source: ScienceNOW - September 17, 2020 Category: Science Authors: Cheng, J., Lau, B., La Venuta, G., Ameismeier, M., Berninghausen, O., Hurt, E., Beckmann, R. Tags: Biochemistry r-articles Source Type: news

Cryo-EM structure of 90S small ribosomal subunit precursors in transition states
The 90S preribosome is a large, early assembly intermediate of small ribosomal subunits that undergoes structural changes to give a pre-40S ribosome. Here, we gained insight into this transition by determining cryo–electron microscopy structures of Saccharomyces cerevisiae intermediates in the path from the 90S to the pre-40S. The full transition is blocked by deletion of RNA helicase Dhr1. A series of structural snapshots revealed that the excised 5' external transcribed spacer (5' ETS) is degraded within 90S, driving stepwise disassembly of assembly factors and ribosome maturation. The nuclear exosome, an RNA degra...
Source: ScienceNOW - September 17, 2020 Category: Science Authors: Du, Y., An, W., Zhu, X., Sun, Q., Qi, J., Ye, K. Tags: Biochemistry reports Source Type: news

Structure-based design of prefusion-stabilized SARS-CoV-2 spikes
The coronavirus disease 2019 (COVID-19) pandemic has led to accelerated efforts to develop therapeutics and vaccines. A key target of these efforts is the spike (S) protein, which is metastable and difficult to produce recombinantly. We characterized 100 structure-guided spike designs and identified 26 individual substitutions that increased protein yields and stability. Testing combinations of beneficial substitutions resulted in the identification of HexaPro, a variant with six beneficial proline substitutions exhibiting higher expression than its parental construct (by a factor of 10) as well as the ability to withstand...
Source: ScienceNOW - September 17, 2020 Category: Science Authors: Hsieh, C.-L., Goldsmith, J. A., Schaub, J. M., DiVenere, A. M., Kuo, H.-C., Javanmardi, K., Le, K. C., Wrapp, D., Lee, A. G., Liu, Y., Chou, C.-W., Byrne, P. O., Hjorth, C. K., Johnson, N. V., Ludes-Meyers, J., Nguyen, A. W., Park, J., Wang, N., Amengor, Tags: Biochemistry, Virology reports Source Type: news

Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we report a humanized monoclonal antibody, H014, that efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nanomolar concentrations by engaging the spike (S) receptor binding domain (RBD). H014 administration reduced SARS-CoV-2 titers in infected lungs and prevented pulmonary pathology in a human angiotensin-converting enzyme 2 mouse ...
Source: ScienceNOW - September 17, 2020 Category: Science Authors: Lv, Z., Deng, Y.-Q., Ye, Q., Cao, L., Sun, C.-Y., Fan, C., Huang, W., Sun, S., Sun, Y., Zhu, L., Chen, Q., Wang, N., Nie, J., Cui, Z., Zhu, D., Shaw, N., Li, X.-F., Li, Q., Xie, L., Wang, Y., Rao, Z., Qin, C.-F., Wang, X. Tags: Biochemistry, Microbiology reports Source Type: news

Creating diamond devices to detect Parkinson's early
(Michigan State University) Michigan State University researchers are leading an effort to use innovative diamond devices to monitor the brain's biochemistry for early warning signs of disease. (Source: EurekAlert! - Medicine and Health)
Source: EurekAlert! - Medicine and Health - September 11, 2020 Category: International Medicine & Public Health Source Type: news

LSU Health study 1st to show nonharmful stress protects against disease in offspring
(Louisiana State University Health Sciences Center) Research led by Jeff Gidday, PhD, Professor of Ophthalmology, Biochemistry, Neuroscience, and Physiology at LSU Health New Orleans School of Medicine, reports what is believed to be the first study in a mammalian model documenting the reprogramming of heritability to promote disease resilience in the next generation. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - September 10, 2020 Category: Biology Source Type: news

Coupling transcription and translation
(Source: ScienceNOW)
Source: ScienceNOW - September 10, 2020 Category: Science Authors: Vinson, V. Tags: Biochemistry, Molecular Biology twis Source Type: news

A gateway to the cytosol
(Source: ScienceNOW)
Source: ScienceNOW - September 10, 2020 Category: Science Authors: Hurtley, S. M. Tags: Biochemistry, Microbiology twis Source Type: news

Structural basis of transcription-translation coupling and collision in bacteria
Prokaryotic messenger RNAs (mRNAs) are translated as they are transcribed. The lead ribosome potentially contacts RNA polymerase (RNAP) and forms a supramolecular complex known as the expressome. The basis of expressome assembly and its consequences for transcription and translation are poorly understood. Here, we present a series of structures representing uncoupled, coupled, and collided expressome states determined by cryo–electron microscopy. A bridge between the ribosome and RNAP can be formed by the transcription factor NusG, which stabilizes an otherwise-variable interaction interface. Shortening of the interv...
Source: ScienceNOW - September 10, 2020 Category: Science Authors: Webster, M. W., Takacs, M., Zhu, C., Vidmar, V., Eduljee, A., Abdelkareem, M., Weixlbaumer, A. Tags: Biochemistry reports Source Type: news

Structural basis of transcription-translation coupling
In bacteria, transcription and translation are coupled processes in which the movement of RNA polymerase (RNAP)–synthesizing messenger RNA (mRNA) is coordinated with the movement of the first ribosome-translating mRNA. Coupling is modulated by the transcription factors NusG (which is thought to bridge RNAP and the ribosome) and NusA. Here, we report cryo–electron microscopy structures of Escherichia coli transcription-translation complexes (TTCs) containing different-length mRNA spacers between RNAP and the ribosome active-center P site. Structures of TTCs containing short spacers show a state incompatible with...
Source: ScienceNOW - September 10, 2020 Category: Science Authors: Wang, C., Molodtsov, V., Firlar, E., Kaelber, J. T., Blaha, G., Su, M., Ebright, R. H. Tags: Biochemistry, Molecular Biology reports Source Type: news

A molecular pore spans the double membrane of the coronavirus replication organelle
In this study, we used cellular cryo–electron microscopy to visualize a molecular pore complex that spans both membranes of the double-membrane vesicle and would allow export of RNA to the cytosol. A hexameric assembly of a large viral transmembrane protein was found to form the core of the crown-shaped complex. This coronavirus-specific structure likely plays a key role in coronavirus replication and thus constitutes a potential drug target. (Source: ScienceNOW)
Source: ScienceNOW - September 10, 2020 Category: Science Authors: Wolff, G., Limpens, R. W. A. L., Zevenhoven-Dobbe, J. C., Laugks, U., Zheng, S., de Jong, A. W. M., Koning, R. I., Agard, D. A., Grünewald, K., Koster, A. J., Snijder, E. J., Barcena, M. Tags: Biochemistry, Microbiology reports Source Type: news

Protein causes mutations that lead to breast cancer cell aggression
(University of Alberta Faculty of Medicine& Dentistry) In her previous research, University of Alberta biochemist Ing Swie Goping identified that the protein, BCL-2 interacting killer (BIK), was associated with relapses in breast cancer patients. In a new study published in the journal Cell Death and Disease, she found that the problem lies with the cellular 'self-destruct' process of apoptosis. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - September 8, 2020 Category: Biology Source Type: news

Are aliens hiding in plain sight?
Several missions this year are seeking out life on the red planet. But would we recognise extraterrestrials if we found them?In July, three unmanned missions blasted off to Mars – from China (Tianwen-1), the US (Nasa ’s Mars 2020 Perseverance Rover) and the United Arab Emirates (Hope). The Chinese and American missions have lander craft that will seek signs of current or past life on Mars. Nasa is also planning to send itsEuropa Clipper probe to survey Jupiter ’s moon Europa, and the robotic landerDragonfly to Saturn ’s moon Titan. Both moons are widely thought to be promising hunting grounds for li...
Source: Guardian Unlimited Science - September 5, 2020 Category: Science Authors: Philip Ball Tags: Alien life Science Mars Space Biology Saturn Jupiter Astronomy Biochemistry and molecular biology Zoology Source Type: news

Can proteins be truly designed sans function?
(Source: ScienceNOW)
Source: ScienceNOW - September 3, 2020 Category: Science Authors: Peacock, A. Tags: Biochemistry perspective Source Type: news

Finding the start
(Source: ScienceNOW)
Source: ScienceNOW - September 3, 2020 Category: Science Authors: Vinson, V. Tags: Biochemistry, Molecular Biology twis Source Type: news

A viral block on host protein synthesis
(Source: ScienceNOW)
Source: ScienceNOW - September 3, 2020 Category: Science Authors: Vinson, V. Tags: Biochemistry, Microbiology twis Source Type: news

Reconstituting autophagosome nucleation
(Source: ScienceNOW)
Source: ScienceNOW - September 3, 2020 Category: Science Authors: Hurtley, S. M. Tags: Biochemistry, Cell Biology twis Source Type: news

A new tool in the protein design toolbox
(Source: ScienceNOW)
Source: ScienceNOW - September 3, 2020 Category: Science Authors: Vinson, V. Tags: Biochemistry, Chemistry twis Source Type: news

A decoy receptor for SARS-CoV-2
(Source: ScienceNOW)
Source: ScienceNOW - September 3, 2020 Category: Science Authors: Vinson, V. Tags: Biochemistry, Microbiology twis Source Type: news

Structure of a human 48S translational initiation complex
A key step in translational initiation is the recruitment of the 43S preinitiation complex by the cap-binding complex [eukaryotic initiation factor 4F (eIF4F)] at the 5' end of messenger RNA (mRNA) to form the 48S initiation complex (i.e., the 48S). The 48S then scans along the mRNA to locate a start codon. To understand the mechanisms involved, we used cryo–electron microscopy to determine the structure of a reconstituted human 48S. The structure reveals insights into early events of translation initiation complex assembly, as well as how eIF4F interacts with subunits of eIF3 near the mRNA exit channel in the 43S. T...
Source: ScienceNOW - September 3, 2020 Category: Science Authors: Brito Querido, J., Sokabe, M., Kraatz, S., Gordiyenko, Y., Skehel, J. M., Fraser, C. S., Ramakrishnan, V. Tags: Biochemistry, Molecular Biology r-articles Source Type: news

A defined structural unit enables de novo design of small-molecule-binding proteins
The de novo design of proteins that bind highly functionalized small molecules represents a great challenge. To enable computational design of binders, we developed a unit of protein structure—a van der Mer (vdM)—that maps the backbone of each amino acid to statistically preferred positions of interacting chemical groups. Using vdMs, we designed six de novo proteins to bind the drug apixaban; two bound with low and submicromolar affinity. X-ray crystallography and mutagenesis confirmed a structure with a precisely designed cavity that forms favorable interactions in the drug–protein complex. vdMs may enab...
Source: ScienceNOW - September 3, 2020 Category: Science Authors: Polizzi, N. F., DeGrado, W. F. Tags: Biochemistry, Chemistry r-articles Source Type: news

Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. A major virulence factor of SARS-CoVs is the nonstructural protein 1 (Nsp1), which suppresses host gene expression by ribosome association. Here, we show that Nsp1 from SARS-CoV-2 binds to the 40S ribosomal subunit, resulting in shutdown of messenger RNA (mRNA) translation both in vitro and in cells. Structural analysis by cryo–electron microscopy of in vitro–reconstituted Nsp1-40S and various native Nsp1-40S and -80S complexes revealed that the Nsp1 C terminus binds t...
Source: ScienceNOW - September 3, 2020 Category: Science Authors: Thoms, M., Buschauer, R., Ameismeier, M., Koepke, L., Denk, T., Hirschenberger, M., Kratzat, H., Hayn, M., Mackens-Kiani, T., Cheng, J., Straub, J. H., Stürzel, C. M., Fröhlich, T., Berninghausen, O., Becker, T., Kirchhoff, F., Sparrer, K. Tags: Biochemistry, Microbiology reports Source Type: news

Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2
The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds angiotensin-converting enzyme 2 (ACE2) on host cells to initiate entry, and soluble ACE2 is a therapeutic candidate that neutralizes infection by acting as a decoy. By using deep mutagenesis, mutations in ACE2 that increase S binding are found across the interaction surface, in the asparagine 90–glycosylation motif and at buried sites. The mutational landscape provides a blueprint for understanding the specificity of the interaction between ACE2 and S and for engineering high-affinity decoy receptors. Combining mutations gives...
Source: ScienceNOW - September 3, 2020 Category: Science Authors: Chan, K. K., Dorosky, D., Sharma, P., Abbasi, S. A., Dye, J. M., Kranz, D. M., Herbert, A. S., Procko, E. Tags: Biochemistry, Microbiology reports Source Type: news

Reconstitution of autophagosome nucleation defines Atg9 vesicles as seeds for membrane formation
In this study, we reconstituted autophagosome nucleation using recombinant components from yeast. We found that Atg9 proteoliposomes first recruited the phosphatidylinositol 3-phosphate kinase complex, followed by Atg21, the Atg2-Atg18 lipid transfer complex, and the E3-like Atg12–Atg5-Atg16 complex, which promoted Atg8 lipidation. Furthermore, we found that Atg2 could transfer lipids for Atg8 lipidation. In selective autophagy, these reactions could potentially be coupled to the cargo via the Atg19-Atg11-Atg9 interactions. We thus propose that Atg9 vesicles form seeds that establish membrane contact sites to initiat...
Source: ScienceNOW - September 3, 2020 Category: Science Authors: Sawa-Makarska, J., Baumann, V., Coudevylle, N., von Bülow, S., Nogellova, V., Abert, C., Schuschnig, M., Graef, M., Hummer, G., Martens, S. Tags: Biochemistry, Cell Biology, Online Only r-articles Source Type: news

NIDCR's Fall 2020 E-Newsletter
Having trouble viewing this email? View it as a Web page. NIDCR's Fall 2020 E-Newsletter In this issue: NIDCR News Funding Opportunities NIH/HHS News Funding Notices Science Advances Subscribe to NICDR News Grantee News   NIDCR News NIDCR Announces Availability of COVID-19 Research Funding On May 5, NIDCR issued two Notices of Special Interest highlighting the urgent need for research on coronavirus disease 2019. This research may be conducted either via the National Dental PBRN infrastructu...
Source: NIDCR Science News - September 1, 2020 Category: Dentistry Source Type: news

Antiviral used to treat cat coronavirus also works against SARS-CoV-2
Researchers at the University of Alberta are preparing to launch clinical trials of a drug used to cure a deadly disease caused by a coronavirus in cats that they expect will also be effective as a treatment for humans against COVID-19. "In just two months, our results have shown that the drug is effective at inhibiting viral replication in cells with SARS-CoV-2," said Joanne Lemieux, a professor of biochemistry in the Faculty of Medicine & Dentistry. (Source: World Pharma News)
Source: World Pharma News - August 27, 2020 Category: Pharmaceuticals Tags: Featured Research Research and Development Source Type: news

A synthetic synaptic organizer protein restores glutamatergic neuronal circuits
Neuronal synapses undergo structural and functional changes throughout life, which are essential for nervous system physiology. However, these changes may also perturb the excitatory–inhibitory neurotransmission balance and trigger neuropsychiatric and neurological disorders. Molecular tools to restore this balance are highly desirable. Here, we designed and characterized CPTX, a synthetic synaptic organizer combining structural elements from cerebellin-1 and neuronal pentraxin-1. CPTX can interact with presynaptic neurexins and postsynaptic AMPA-type ionotropic glutamate receptors and induced the formation of excita...
Source: ScienceNOW - August 27, 2020 Category: Science Authors: Suzuki, K., Elegheert, J., Song, I., Sasakura, H., Senkov, O., Matsuda, K., Kakegawa, W., Clayton, A. J., Chang, V. T., Ferrer-Ferrer, M., Miura, E., Kaushik, R., Ikeno, M., Morioka, Y., Takeuchi, Y., Shimada, T., Otsuka, S., Stoyanov, S., Watanabe, M., T Tags: Biochemistry, Neuroscience, Online Only r-articles Source Type: news

Expanding the space of protein geometries by computational design of de novo fold families
We present a computational design method, loop-helix-loop unit combinatorial sampling (LUCS), that mimics nature’s ability to create families of proteins with the same overall fold but precisely tunable geometries. Through near-exhaustive sampling of loop-helix-loop elements, LUCS generates highly diverse geometries encompassing those found in nature but also surpassing known structure space. Biophysical characterization showed that 17 (38%) of 45 tested LUCS designs encompassing two different structural topologies were well folded, including 16 with designed non-native geometries. Four experimentally solved structur...
Source: ScienceNOW - August 27, 2020 Category: Science Authors: Pan, X., Thompson, M. C., Zhang, Y., Liu, L., Fraser, J. S., Kelly, M. J. S., Kortemme, T. Tags: Biochemistry reports Source Type: news

Structural basis of a shared antibody response to SARS-CoV-2
Molecular understanding of neutralizing antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could accelerate vaccine design and drug discovery. We analyzed 294 anti–SARS-CoV-2 antibodies and found that immunoglobulin G heavy-chain variable region 3-53 (IGHV3-53) is the most frequently used IGHV gene for targeting the receptor-binding domain (RBD) of the spike protein. Co-crystal structures of two IGHV3-53–neutralizing antibodies with RBD, with or without Fab CR3022, at 2.33- to 3.20-angstrom resolution revealed that the germline-encoded residues dominate recognition of the angiote...
Source: ScienceNOW - August 27, 2020 Category: Science Authors: Yuan, M., Liu, H., Wu, N. C., Lee, C.-C. D., Zhu, X., Zhao, F., Huang, D., Yu, W., Hua, Y., Tien, H., Rogers, T. F., Landais, E., Sok, D., Jardine, J. G., Burton, D. R., Wilson, I. A. Tags: Biochemistry, Immunology reports Source Type: news

A nitrogenase-like enzyme system catalyzes methionine, ethylene, and methane biogenesis
Bacterial production of gaseous hydrocarbons such as ethylene and methane affects soil environments and atmospheric climate. We demonstrate that biogenic methane and ethylene from terrestrial and freshwater bacteria are directly produced by a previously unknown methionine biosynthesis pathway. This pathway, present in numerous species, uses a nitrogenase-like reductase that is distinct from known nitrogenases and nitrogenase-like reductases and specifically functions in C–S bond breakage to reduce ubiquitous and appreciable volatile organic sulfur compounds such as dimethyl sulfide and (2-methylthio)ethanol. Liberate...
Source: ScienceNOW - August 27, 2020 Category: Science Authors: North, J. A., Narrowe, A. B., Xiong, W., Byerly, K. M., Zhao, G., Young, S. J., Murali, S., Wildenthal, J. A., Cannon, W. R., Wrighton, K. C., Hettich, R. L., Tabita, F. R. Tags: Biochemistry, Microbiology reports Source Type: news

Architecture of a catalytically active homotrimeric plant cellulose synthase complex
Cellulose is an essential plant cell wall component and represents the most abundant biopolymer on Earth. Supramolecular plant cellulose synthase complexes organize multiple linear glucose polymers into microfibrils as load-bearing wall components. We determined the structure of a poplar cellulose synthase CesA homotrimer that suggests a molecular basis for cellulose microfibril formation. This complex, stabilized by cytosolic plant-conserved regions and helical exchange within the transmembrane segments, forms three channels occupied by nascent cellulose polymers. Secretion steers the polymers toward a common exit point, ...
Source: ScienceNOW - August 27, 2020 Category: Science Authors: Purushotham, P., Ho, R., Zimmer, J. Tags: Biochemistry, Ecology r-articles Source Type: news

A common theme in antibody responses
(Source: ScienceNOW)
Source: ScienceNOW - August 27, 2020 Category: Science Authors: Vinson, V. Tags: Biochemistry, Immunology twis Source Type: news

Soil sulfur metabolism surprise
(Source: ScienceNOW)
Source: ScienceNOW - August 27, 2020 Category: Science Authors: Funk, M. A. Tags: Biochemistry, Microbiology twis Source Type: news

Synthetic excitatory synaptic organizer
(Source: ScienceNOW)
Source: ScienceNOW - August 27, 2020 Category: Science Authors: Hurtley, S. M. Tags: Biochemistry, Neuroscience twis Source Type: news

Exploring the design landscape
(Source: ScienceNOW)
Source: ScienceNOW - August 27, 2020 Category: Science Authors: Vinson, V. Tags: Biochemistry twis Source Type: news

Plant cell wall construction crew
(Source: ScienceNOW)
Source: ScienceNOW - August 27, 2020 Category: Science Authors: Funk, M. A. Tags: Biochemistry, Ecology twis Source Type: news