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 for the 3' ...
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-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

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