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.
Immunology: Mind the immuno-connection gap
April 24th, 2017 by Wolfgang Link
Nature Chemical Biology 13, 572 (2017). doi:10.1038/nchembio.2373
Author: Wolfgang Link
Biologic drugs that modulate the immune system have revolutionized the therapeutic landscape for several selected cancer types. A new study reports an image-based assay system to monitor cell–cell interactions, identifying small-molecule compounds with immunomodulatory capacity.
Redox-Sensitive MarR Homologue BifR from Burkholderia thailandensis Regulates Biofilm Formation
April 21st, 2017 by Ashish Gupta, Stanley M. Fuentes and Anne Grove
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
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.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
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
Deep Sequencing Analysis of Aptazyme Variants Based on a Pistol Ribozyme
April 14th, 2017 by Shungo Kobori, Kei Takahashi and Yohei Yokobayashi
The chemical basis for electrical signaling
April 13th, 2017 by William A Catterall
Nature Chemical Biology 13, 455 (2017). doi:10.1038/nchembio.2353
Authors: William A Catterall, Goragot Wisedchaisri & Ning Zheng
Anti-Bacterials: Out-SMARting drug resistance
April 13th, 2017 by Alison Farrell
Nature Chemical Biology 13, 451 (2017). doi:10.1038/nchembio.2368
Author: Alison Farrell