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
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
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
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 readin...
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
The glassiness of hardening protein droplets
(Source: ScienceNOW)
Source: ScienceNOW - December 10, 2020 Category: Science Authors: Zhang, H. Tags: Biochemistry perspective Source Type: news
A decline in the carbon fertilization effect
(Source: ScienceNOW)
Source: ScienceNOW - December 10, 2020 Category: Science Authors: Sugden, A. M. Tags: Biochemistry, Ecology twis Source Type: news
From phenotype to structure
(Source: ScienceNOW)
Source: ScienceNOW - December 10, 2020 Category: Science Authors: Vinson, V. Tags: Biochemistry, Engineering twis Source Type: news
Rheology of aging protein condensates
(Source: ScienceNOW)
Source: ScienceNOW - December 10, 2020 Category: Science Authors: Lavine, M. S. Tags: Biochemistry twis Source Type: news
Recent global decline of CO2 fertilization effects on vegetation photosynthesis
The enhanced vegetation productivity driven by increased concentrations of carbon dioxide (CO2) [i.e., the CO2 fertilization effect (CFE)] sustains an important negative feedback on climate warming, but the temporal dynamics of CFE remain unclear. Using multiple long-term satellite- and ground-based datasets, we showed that global CFE has declined across most terrestrial regions of the globe from 1982 to 2015, correlating well with changing nutrient concentrations and availability of soil water. Current carbon cycle models also demonstrate a declining CFE trend, albeit one substantially weaker than that from the global obs...
Source: ScienceNOW - December 10, 2020 Category: Science Authors: Wang, S., Zhang, Y., Ju, W., Chen, J. M., Ciais, P., Cescatti, A., Sardans, J., Janssens, I. A., Wu, M., Berry, J. A., Campbell, E., Fernandez-Martinez, M., Alkama, R., Sitch, S., Friedlingstein, P., Smith, W. K., Yuan, W., He, W., Lombardozzi, D., Kautz, Tags: Biochemistry, Ecology 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
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
RUDN University medics created a wound-healing gel with metabolic products of trichoderma
(RUDN University) Researchers from the Department of Biochemistry of RUDN University developed a wound-healing gel based on a substance that is produced by Trichoderma fungi. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - December 4, 2020 Category: Biology Source Type: news
Hidden structure found in essential metabolic machinery
(Rice University) Rice University biochemists have discovered membrane-divided subcompartments within organelles called peroxisomes, essential pieces of metabolic machinery for all higher order life from yeast to humans. The research appears this week in Nature Communications. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - December 4, 2020 Category: Biology Source Type: news
Tetrameric immune receptors
(Source: ScienceNOW)
Source: ScienceNOW - December 3, 2020 Category: Science Authors: Hines, P. J. Tags: Biochemistry twis Source Type: news
