Protein degradation: DCAFinating splicing

April 24th, 2017 by Georg E Winter

Nature Chemical Biology 13, 575 (2017). doi:10.1038/nchembio.2378

Author: Georg E Winter

Chemical control of protein homeostasis and induction of protein destabilization are emerging therapeutic strategies. Two recent studies identify a set of sulfonamides that can modulate the CRL4DCAF15 E3 ligase complex to target the splicing factor RBM39 for proteasomal degradation.

Global survey of the immunomodulatory potential of common drugs

April 24th, 2017 by Gregory I Vladimer

Nature Chemical Biology 13, 681 (2017). doi:10.1038/nchembio.2360

Authors: Gregory I Vladimer, Berend Snijder, Nikolaus Krall, Johannes W Bigenzahn, Kilian V M Huber, Charles-Hugues Lardeau, Kumar Sanjiv, Anna Ringler, Ulrika Warpman Berglund, Monika Sabler, Oscar Lopez de la Fuente, Paul Knöbl, Stefan Kubicek, Thomas Helleday, Ulrich Jäger & Giulio Superti-Furga

Selective degradation of splicing factor CAPERα by anticancer sulfonamides

April 24th, 2017 by Taisuke Uehara

Nature Chemical Biology 13, 675 (2017). doi:10.1038/nchembio.2363

Authors: Taisuke Uehara, Yukinori Minoshima, Koji Sagane, Naoko Hata Sugi, Kaoru Ogawa Mitsuhashi, Noboru Yamamoto, Hiroshi Kamiyama, Kentaro Takahashi, Yoshihiko Kotake, Mai Uesugi, Akira Yokoi, Atsushi Inoue, Taku Yoshida, Miyuki Mabuchi, Akito Tanaka & Takashi Owa

  • Posted in Nat Chem Biol, Publications
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Redox-Sensitive MarR Homologue BifR from Burkholderia thailandensis Regulates Biofilm Formation

April 21st, 2017 by Ashish Gupta, Stanley M. Fuentes and Anne Grove

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Biochemistry
DOI: 10.1021/acs.biochem.7b00103

Two Distinct Assembly States of the Cysteine Regulatory Complex of Salmonella typhimurium Are Regulated by Enzyme–Substrate Cognate Pairs

April 21st, 2017 by Abhishek Kaushik, Mary Krishna Ekka and Sangaralingam Kumaran

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Biochemistry
DOI: 10.1021/acs.biochem.6b01204

Disease-Associated Extracellular Loop Mutations in the Adhesion G Protein-Coupled Receptor G1 (ADGRG1; GPR56) Differentially Regulate Downstream Signaling [Molecular Bases of Disease]

April 19th, 2017 by Ayush Kishore, Randy A. Hall

Mutations to the adhesion G protein-coupled receptor ADGRG1 (G1; also known as GPR56) underlie the neurological disorder bilateral frontoparietal polymicrogyria (BFPP). Disease-associated mutations in G1 studied to date are believed to induce complete loss of receptor function, either through disruption of receptor trafficking or signaling activity. Given that N-terminal truncation of G1 and other adhesion G protein-coupled receptors has been shown to significantly increase the receptors' constitutive signaling, we examined two different BFPP-inducing extracellular loop mutations (R565W and L640R) in the context of both full-length and N-terminally truncated (deltaNT) G1. Interestingly, we found that these mutations reduced surface expression of full-length G1 but not G1-deltaNT in HEK-293 cells. Moreover, the mutations ablated receptor-mediated activation of serum response factor luciferase, a classic measure of Galpha12/13-mediated signaling, but had no effect on G1-mediated signaling to nuclear factor of activated T cells (NFAT) luciferase. Given these differential signaling results, we sought to further elucidate the pathway by which G1 can activate NFAT luciferase. We found no evidence that deltaNT activation of NFAT is dependent on Galphaq/11-mediated or beta-arrestin-mediated signaling, but rather involves liberation of G beta gamma subunits and activation of calcium channels. These findings reveal that disease-associated mutations to the extracellular loops of G1 differentially alter receptor trafficking, depending on the presence of the N-terminus, and also differentially alter signaling to distinct downstream pathways.
  • Posted in Journal of Biological Chemistry, Publications
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Using the pimeloyl-CoA synthetase adenylation fold to synthesize fatty acid thioesters

April 17th, 2017 by Menglu Wang

Nature Chemical Biology 13, 660 (2017). doi:10.1038/nchembio.2361

Authors: Menglu Wang, Lucile Moynié, Peter J Harrison, Van Kelly, Andrew Piper, James H Naismith & Dominic J Campopiano

  • Posted in Nat Chem Biol, Publications
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The pimeloyl-CoA synthetase BioW defines a new fold for adenylate-forming enzymes

April 17th, 2017 by Paola Estrada

Nature Chemical Biology 13, 668 (2017). doi:10.1038/nchembio.2359

Authors: Paola Estrada, Miglena Manandhar, Shi-Hui Dong, Jaigeeth Deveryshetty, Vinayak Agarwal, John E Cronan & Satish K Nair

  • Posted in Nat Chem Biol, Publications
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Deep Sequencing Analysis of Aptazyme Variants Based on a Pistol Ribozyme

April 14th, 2017 by Shungo Kobori, Kei Takahashi and Yohei Yokobayashi

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ACS Synthetic Biology
DOI: 10.1021/acssynbio.7b00057

Optogenetics: Lighting up kinases

April 13th, 2017 by Grant Miura

Nature Chemical Biology 13, 451 (2017). doi:10.1038/nchembio.2365

Author: Grant Miura