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
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-head binding. The pre...
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
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
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
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
