Kinesin takes substeps
(Source: ScienceNOW)
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Jiang, D. Tags: Biochemistry, Materials Science twis Source Type: news

Comment on "Structural evidence for a dynamic metallocofactor during N2 reduction by Mo-nitrogenase"
Kang et al. (Reports, 19 June 2020, p. 1381) report a structure of the nitrogenase MoFe protein that is interpreted to indicate binding of N2 or an N2-derived species to the active-site FeMo cofactor. Independent refinement of the structure and consideration of biochemical evidence do not support this claim. (Source: ScienceNOW)
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Peters, J. W., Einsle, O., Dean, D. R., DeBeer, S., Hoffman, B. M., Holland, P. L., Seefeldt, L. C. Tags: Biochemistry t-comment Source Type: news

Response to Comment on "Structural evidence for a dynamic metallocofactor during N2 reduction by Mo-nitrogenase"
Peters et al. comment on our report of the dynamic structure of the nitrogenase metallocofactor during N2 reduction. Their claim that their independent structural refinement and consideration of biochemical data contradict our finding is incorrect and is strongly refuted by our biochemical and structural data that collectively and conclusively point to the binding of dinitrogen species to the nitrogenase cofactor. (Source: ScienceNOW)
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Kang, W., Lee, C. C., Jasniewski, A. J., Ribbe, M. W., Hu, Y. Tags: Biochemistry t-comment Source Type: news

Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape
In this study, we generated four neutralizing nanobodies that target the receptor binding domain of the SARS-CoV-2 spike protein. We used x-ray crystallography and cryo–electron microscopy to define two distinct binding epitopes. On the basis of these structures, we engineered multivalent nanobodies with more than 100 times the neutralizing activity of monovalent nanobodies. Biparatopic nanobody fusions suppressed the emergence of escape mutants. Several nanobody constructs neutralized through receptor binding competition, whereas other monovalent and biparatopic nanobodies triggered aberrant activation of the spike ...
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Koenig, P.-A., Das, H., Liu, H., Kümmerer, B. M., Gohr, F. N., Jenster, L.-M., Schiffelers, L. D. J., Tesfamariam, Y. M., Uchima, M., Wuerth, J. D., Gatterdam, K., Ruetalo, N., Christensen, M. H., Fandrey, C. I., Normann, S., Tödtmann, J. Tags: Biochemistry, Microbiology, Online Only r-articles Source Type: news

Germanium nanospheres for ultraresolution picotensiometry of kinesin motors
Kinesin motors are essential for the transport of cellular cargo along microtubules. How the motors step, detach, and cooperate with each other is still unclear. To dissect the molecular motion of kinesin-1, we developed germanium nanospheres as ultraresolution optical trapping probes. We found that single motors took 4-nanometer center-of-mass steps. Furthermore, kinesin-1 never detached from microtubules under hindering load conditions. Instead, it slipped on microtubules in microsecond-long, 8-nanometer steps and remained in this slip state before detaching or reengaging in directed motion. Unexpectedly, reengagement an...
Source: ScienceNOW - February 11, 2021 Category: Science Authors: Sudhakar, S., Abdosamadi, M. K., Jachowski, T. J., Bugiel, M., Jannasch, A., Schäffer, E. Tags: Biochemistry, Materials Science, Online Only r-articles Source Type: news

Regular walnut consumption may reduce negative outcomes of H. pylori infection
(Edelman Public Relations, Seattle) A new animal study, published in theJournal of Clinical Biochemistry and Nutrition, suggests regular walnut consumption may be a promising intervention for reducing negative outcomes associated with Helicobacter pylori (H. pylori) infection, a widespread bacterial infection that affects more than half of the world's population. (Source: EurekAlert! - Infectious and Emerging Diseases)
Source: EurekAlert! - Infectious and Emerging Diseases - February 9, 2021 Category: Infectious Diseases Source Type: news

NIH Director Francis Collins Is Fighting This Coronavirus While Preparing for the Next One
In May 2020, Dr. Francis Collins, the longtime head of the National Institutes of Health (NIH), was called to the White House to meet with Jared Kushner, the then President’s son-in-law and adviser, and Dr. Deborah Birx, the head of the White House Coronavirus Task Force. A few weeks earlier, Congress had given the NIH $1.5 billion to try to speed up the process of developing new diagnostic tests for COVID-19, and the White House, which was dubious about increasing the rate of testing, wanted to know more about what the NIH was doing. Collins is technically the boss of Dr. Anthony Fauci, but during the pandemic he ha...
Source: TIME: Health - February 4, 2021 Category: Consumer Health News Authors: Belinda Luscombe Tags: Uncategorized COVID-19 feature Magazine Source Type: news

Poly(A) and RNA: More ways to interact
(Source: ScienceNOW)
Source: ScienceNOW - February 4, 2021 Category: Science Authors: Jiang, D. Tags: Biochemistry twis Source Type: news

RNA stabilization by a poly(A) tail 3'-end binding pocket and other modes of poly(A)-RNA interaction
Polyadenylate [poly(A)] tail addition to the 3' end of a wide range of RNAs is a highly conserved modification that plays a central role in cellular RNA function. Elements for nuclear expression (ENEs) are cis-acting RNA elements that stabilize poly(A) tails by sequestering them in RNA triplex structures. A crystal structure of a double ENE from a rice hAT transposon messenger RNA complexed with poly(A)28 at a resolution of 2.89 angstroms reveals multiple modes of interaction with poly(A), including major-groove triple helices, extended minor-groove interactions with RNA double helices, a quintuple-base motif that transiti...
Source: ScienceNOW - February 4, 2021 Category: Science Authors: Torabi, S.-F., Vaidya, A. T., Tycowski, K. T., DeGregorio, S. J., Wang, J., Shu, M.-D., Steitz, T. A., Steitz, J. A. Tags: Biochemistry, Online Only r-articles Source Type: news

UTEP fights superbugs with $1.2 Million NIH grant to produce antibiotics
(University of Texas at El Paso) Chu-Young Kim, Ph.D., associate professor of chemistry and biochemistry at The University of Texas at El Paso, is helping combat the threat of superbugs - illnesses caused by drug-resistant bacteria -- by returning to nature.His work is supported by a $1.2 million grant from the National Institutes of Health (NIH) to develop a biological method for producing new versions of current antibiotics that have become ineffective due to resistance.Superbugs are a major problem threatening the lives and health of people worldwide. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - February 2, 2021 Category: Biology Source Type: news

Toho university scientists find new mechanism to keep cell death pathway suppressed
(Toho University) A research group led by Prof. Hiroyasu Nakano at the Department of Biochemistry, Toho University Faculty of Medicine, identified Mind bomb-2 (MIB2) as an enzyme that ubiquitinates and modifies the protein cFLIP, which plays a central role in suppressing cell death. This finding indicates that ubiquitination of cFLIP by MIB2 plays an essential role in suppressing caspase 8-mediated cell death, suggesting that ubiquitination of cFLIP may be a promising target for development of therapies to control cell death. (Source: EurekAlert! - Biology)
Source: EurekAlert! - Biology - January 27, 2021 Category: Biology Source Type: news

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 holder for CABENUVA.C...
Source: Johnson and Johnson - January 22, 2021 Category: Pharmaceuticals Tags: Innovation 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

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

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