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Nature Chemical Biology

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https://www.readbyqxmd.com/read/30177848/chemical-proteomics-reveals-new-targets-of-cysteine-sulfinic-acid-reductase
#1
Salma Akter, Ling Fu, Youngeun Jung, Mauro Lo Conte, J Reed Lawson, W Todd Lowther, Rui Sun, Keke Liu, Jing Yang, Kate S Carroll
Cysteine sulfinic acid or S-sulfinylation is an oxidative post-translational modification (OxiPTM) that is known to be involved in redox-dependent regulation of protein function but has been historically difficult to analyze biochemically. To facilitate the detection of S-sulfinylated proteins, we demonstrate that a clickable, electrophilic diazene probe (DiaAlk) enables capture and site-centric proteomic analysis of this OxiPTM. Using this workflow, we revealed a striking difference between sulfenic acid modification (S-sulfenylation) and the S-sulfinylation dynamic response to oxidative stress, which is indicative of different roles for these OxiPTMs in redox regulation...
September 3, 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/30150682/acetate-dependent-trna-acetylation-required-for-decoding-fidelity-in-protein-synthesis
#2
Takaaki Taniguchi, Kenjyo Miyauchi, Yuriko Sakaguchi, Seisuke Yamashita, Akiko Soma, Kozo Tomita, Tsutomu Suzuki
Modification of tRNA anticodons plays a critical role in ensuring accurate translation. N4 -acetylcytidine (ac4 C) is present at the anticodon first position (position 34) of bacterial elongator tRNAMet . Herein, we identified Bacillus subtilis ylbM (renamed tmcAL) as a novel gene responsible for ac4 C34 formation. Unlike general acetyltransferases that use acetyl-CoA, TmcAL activates an acetate ion to form acetyladenylate and then catalyzes ac4 C34 formation through a mechanism similar to tRNA aminoacylation...
August 27, 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/29988068/peptide-exchange-on-mhc-i-by-tapbpr-is-driven-by-a-negative-allostery-release-cycle
#3
Andrew C McShan, Kannan Natarajan, Vlad K Kumirov, David Flores-Solis, Jiansheng Jiang, Mareike Badstübner, Jugmohit S Toor, Clive R Bagshaw, Evgenii L Kovrigin, David H Margulies, Nikolaos G Sgourakis
Chaperones TAPBPR and tapasin associate with class I major histocompatibility complexes (MHC-I) to promote optimization (editing) of peptide cargo. Here, we use solution NMR to investigate the mechanism of peptide exchange. We identify TAPBPR-induced conformational changes on conserved MHC-I molecular surfaces, consistent with our independently determined X-ray structure of the complex. Dynamics present in the empty MHC-I are stabilized by TAPBPR and become progressively dampened with increasing peptide occupancy...
July 9, 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/29988067/noncanonical-translation-via-deadenylated-3-utrs-maintains-primordial-germ-cells
#4
Youngnam N Jin, Peter J Schlueter, Nathalie Jurisch-Yaksi, Pui-Ying Lam, Shan Jin, Woong Y Hwang, Jing-Ruey Joanna Yeh, Masaaki Yoshigi, Shao-En Ong, Monica Schenone, Christina R Hartigan, Steven A Carr, Randall T Peterson
Primordial germ cells (PGCs) form during early embryogenesis with a supply of maternal mRNAs that contain shorter poly(A) tails. How translation of maternal mRNAs is regulated during PGC development remains elusive. Here we describe a small-molecule screen with zebrafish embryos that identified primordazine, a compound that selectively ablates PGCs. Primordazine's effect on PGCs arises from translation repression through primordazine-response elements in the 3' UTRs. Systematic dissection of primordazine's mechanism of action revealed that translation of mRNAs during early embryogenesis occurs by two distinct pathways, depending on the length of their poly(A) tails...
July 9, 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/29988066/painting-translation
#5
Yuichiro Mishima
No abstract text is available yet for this article.
July 9, 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/30224695/t-cell-receptor-cross-reactivity-expanded-by-dramatic-peptide-mhc-adaptability
#6
Timothy P Riley, Lance M Hellman, Marvin H Gee, Juan L Mendoza, Jesus A Alonso, Kendra C Foley, Michael I Nishimura, Craig W Vander Kooi, K Christopher Garcia, Brian M Baker
T cell receptor cross-reactivity allows a fixed T cell repertoire to respond to a much larger universe of potential antigens. Recent work has emphasized the importance of peptide structural and chemical homology, as opposed to sequence similarity, in T cell receptor cross-reactivity. Surprisingly, though, T cell receptors can also cross-react between ligands with little physiochemical commonalities. Studying the clinically relevant receptor DMF5, we demonstrate that cross-recognition of such divergent antigens can occur through mechanisms that involve heretofore unanticipated rearrangements in the peptide and presenting MHC protein, including binding-induced peptide register shifts and extensions from MHC peptide binding grooves...
October 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/30224694/post-translational-site-selective-protein-backbone-%C3%AE-deuteration
#7
Sébastien R G Galan, James R Wickens, Jitka Dadova, Wai-Lung Ng, Xinglong Zhang, Robert A Simion, Robert Quinlan, Elisabete Pires, Robert S Paton, Stephen Caddick, Vijay Chudasama, Benjamin G Davis
Isotopic replacement has long-proven applications in small molecules. However, applications in proteins are largely limited to biosynthetic strategies or exchangeable (for example, N-H/D) labile sites only. The development of postbiosynthetic, C-1 H → C-2 H/D replacement in proteins could enable probing of mechanisms, among other uses. Here we describe a chemical method for selective protein α-carbon deuteration (proceeding from Cys to dehydroalanine (Dha) to deutero-Cys) allowing overall 1 H→2 H/D exchange at a nonexchangeable backbone site...
October 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/30224693/flipping-out-the-peptide
#8
Stephanie Gras
No abstract text is available yet for this article.
October 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/30224692/the-substrate-lends-a-hand
#9
Albert A Bowers
No abstract text is available yet for this article.
October 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/30224691/a-new-target-for-thalidomide
#10
Peter G Wells
No abstract text is available yet for this article.
October 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/30224690/diversifying-bases
#11
Yiyun Song
No abstract text is available yet for this article.
October 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/30224689/fatal-chemoattraction
#12
Mirella Bucci
No abstract text is available yet for this article.
October 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/30224688/cost-benefit-analysis
#13
Grant Miura
No abstract text is available yet for this article.
October 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/30224687/pup-up-the-volume
#14
Caitlin Deane
No abstract text is available yet for this article.
October 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/30190590/sall4-mediates-teratogenicity-as-a-thalidomide-dependent-cereblon-substrate
#15
Mary E Matyskiela, Suzana Couto, Xinde Zheng, Gang Lu, Julia Hui, Katie Stamp, Clifton Drew, Yan Ren, Maria Wang, Aaron Carpenter, Chung-Wein Lee, Thomas Clayton, Wei Fang, Chin-Chun Lu, Mariko Riley, Polat Abdubek, Kate Blease, James Hartke, Gondi Kumar, Rupert Vessey, Mark Rolfe, Lawrence G Hamann, Philip P Chamberlain
Targeted protein degradation via small-molecule modulation of cereblon offers vast potential for the development of new therapeutics. Cereblon-binding therapeutics carry the safety risks of thalidomide, which caused an epidemic of severe birth defects characterized by forelimb shortening or phocomelia. Here we show that thalidomide is not teratogenic in transgenic mice expressing human cereblon, indicating that binding to cereblon is not sufficient to cause birth defects. Instead, we identify SALL4 as a thalidomide-dependent cereblon neosubstrate...
October 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/30177850/establishment-of-the-par-1-cortical-gradient-by-the-apkc-prbh-circuit
#16
Ravikrishna Ramanujam, Ziyin Han, Zhen Zhang, Pakorn Kanchanawong, Fumio Motegi
Cell polarity is the asymmetric compartmentalization of cellular components. An opposing gradient of partitioning-defective protein kinases, atypical protein kinase C (aPKC) and PAR-1, at the cell cortex guides diverse asymmetries in the structure of metazoan cells, but the mechanism underlying their spatial patterning remains poorly understood. Here, we show in Caenorhabditis elegans zygotes that the cortical PAR-1 gradient is patterned as a consequence of dual mechanisms: stabilization of cortical dynamics and protection from aPKC-mediated cortical exclusion...
October 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/30177849/substrate-assisted-enzymatic-formation-of-lysinoalanine-in-duramycin
#17
Linna An, Dillon P Cogan, Claudio D Navo, Gonzalo Jiménez-Osés, Satish K Nair, Wilfred A van der Donk
Duramycin is a heavily post-translationally modified peptide that binds phosphatidylethanolamine. It has been investigated as an antibiotic, an inhibitor of viral entry, a therapeutic for cystic fibrosis, and a tumor and vasculature imaging agent. Duramycin contains a β-hydroxylated Asp (Hya) and four macrocycles, including an essential lysinoalanine (Lal) cross-link. The mechanism of Lal formation is not known. Here we show that Lal is installed stereospecifically by DurN via addition of Lys19 to a dehydroalanine...
October 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/30150681/nuclear-rnr-%C3%AE-antagonizes-cell-proliferation-by-directly-inhibiting-zranb3
#18
Yuan Fu, Marcus J C Long, Somsinee Wisitpitthaya, Huma Inayat, Timothy M Pierpont, Islam M Elsaid, Jordana C Bloom, Joaquin Ortega, Robert S Weiss, Yimon Aye
Since the origins of DNA-based life, the enzyme ribonucleotide reductase (RNR) has spurred proliferation because of its rate-limiting role in de novo deoxynucleoside-triphosphate (dNTP) biosynthesis. Paradoxically, the large subunit, RNR-α, of this obligatory two-component complex in mammals plays a context-specific antiproliferative role. There is little explanation for this dichotomy. Here, we show that RNR-α has a previously unrecognized DNA-replication inhibition function, leading to growth retardation...
October 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/30127387/continuous-directed-evolution-of-proteins-with-improved-soluble-expression
#19
Tina Wang, Ahmed H Badran, Tony P Huang, David R Liu
We report the development of soluble expression phage-assisted continuous evolution (SE-PACE), a system for rapidly evolving proteins with increased soluble expression. Through use of a PACE-compatible AND gate that uses a split-intein pIII, SE-PACE enables two simultaneous positive selections to evolve proteins with improved expression while maintaining their desired activities. In as little as three days, SE-PACE evolved several antibody fragments with >5-fold improvement in expression yield while retaining binding activity...
October 2018: Nature Chemical Biology
https://www.readbyqxmd.com/read/30127386/o-glcnac-modification-of-eif4gi-acts-as-a-translational-switch-in-heat-shock-response
#20
Xingqian Zhang, Xin Erica Shu, Shu-Bing Qian
Heat shock response (HSR) is an ancient signaling pathway leading to thermoprotection of nearly all living organisms. Emerging evidence suggests that intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) serves as a molecular 'thermometer' by reporting ambient temperature fluctuations. Whether and how O-GlcNAc modification regulates HSR remains unclear. Here we report that, upon heat shock stress, the key translation initiation factor eIF4GI undergoes dynamic O-GlcNAcylation at the N-terminal region. Without O-GlcNAc modification, the preferential translation of stress mRNAs is impaired...
October 2018: Nature Chemical Biology
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