ACS DIVISION OF BIOLOGICAL CHEMISTRY

July 18th, 2019 by Mirella Bucci

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0332-4

Freedom to bind

July 18th, 2019 by Yiyun Song

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0335-1

DNA jumps with CRISPR

July 18th, 2019 by Claudio Hetz

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0326-2

Hetz et al. discuss recent advances in the identification and optimization of small molecules targeting the unfolded protein response and the application of these small molecules in cancers, neurodegeneration and metabolic diseases.

July 18th, 2019 by Yiyun Song

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0333-3

Imaging nonsense

July 18th, 2019 by Andreas H. Ludewig

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0321-7

Male C. elegans excrete an N-acylated glutamine that acts via evolutionarily conserved nuclear hormone receptor and chemosensory pathways to counteract dauer diapause and accelerate sexual maturation of hermaphrodites, at the cost of shortening hermaphrodite lifespan.

July 18th, 2019 by Matthew Ravalin

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0322-6

The C termini sequences recognized by E3 ubiquitin ligase CHIP were identified via a peptide library screen. Caspase cleavage caused the exposure of aspartic acid at the C termini of Tau and caspase-6 that made them accessible to CHIP.

July 18th, 2019 by Grant Miura

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0334-2

PROSPECTing for drugs

July 18th, 2019 by Xin Bian

Nature Chemical Biology, Published online: 18 July 2019; doi:10.1038/s41589-019-0325-3

Use of DNA-origami nanostructures to study lipid transfer between closely apposed membrane bilayers supports a model where phospholipids are transferred by extended synaptotagmin 1 between the endoplasmic reticulum and plasma membrane through a shuttle mechanism.

July 15th, 2019 by Matthew W. Boudreau, Jessie Peh, and Paul J. Hergenrother*

July 9th, 2019 by Kevin L. Jagessar, Hassane S. Mchaourab, Derek P. Claxton

As a contributor to multidrug resistance, the family of multidrug and toxin extrusion (MATE) transporters couples the efflux of chemically dissimilar compounds to electrochemical ion gradients. Although divergent transport mechanisms have been proposed for these transporters, previous structural and functional analyses of members of the MATE subfamily DinF suggest that the N-terminal domain (NTD) supports substrate and ion binding. In this report, we investigated the relationship of ligand binding within the NTD to the drug resistance mechanism of the H+-dependent MATE from the hyperthermophilic archaeon Pyrococcus furiosus (PfMATE). To facilitate this study, we developed a cell growth assay in Escherichia coli to characterize the resistance conferred by PfMATE to toxic concentrations of the antimicrobial compound rhodamine 6G. Expression of wild type PfMATE promoted cell growth in the presence of drug, but amino acid substitutions of conserved NTD residues compromised drug resistance. Steady-state binding analysis with purified PfMATE indicated that substrate affinity was unperturbed in these NTD variants. However, exploiting Trp fluorescence as an intrinsic reporter of conformational changes, we found that these variants impaired formation of a unique H+-stabilized structural intermediate. These results imply that disruption of H+ coupling is the origin of compromised toxin resistance in PfMATE variants. These findings support a model mechanism wherein the NTD mediates allosteric coupling to ion gradients through conformational changes to drive substrate transport in PfMATE. Furthermore, the results provide evidence for diverging transport mechanisms within a prokaryotic MATE subfamily.