Rational Modification of a Cross-Linker for Improved Flexible Protein Structure Modeling.

Chemical cross-linking/mass spectrometry (XL-MS) has emerged as a complementary tool for mapping interaction sites within protein networks as well as gaining moderate-resolution native structural insight with minimal interference. XL-MS technology mostly relies on chemoselective reactions (cross-linking) between protein residues and a linker. DSSO represents a versatile cross-linker for protein structure investigation and in-cell XL-MS.

Sodium channels Na1.7, Na1.8 and pain; two distinct mechanisms for Na1.7 null analgesia.

Genetic deletion and pharmacological inhibition are distinct approaches to unravelling pain mechanisms, identifying targets and developing new analgesics. Both approaches have been applied to the voltage-gated sodium channels Na1.7 and Na1.

HSF-1 promotes longevity through ubiquilin-1-dependent mitochondrial network remodelling.

Increased activity of the heat shock factor, HSF-1, suppresses proteotoxicity and enhances longevity. However, the precise mechanisms by which HSF-1 promotes lifespan are unclear. Using an RNAi screen, we identify ubiquilin-1 (ubql-1) as an essential mediator of lifespan extension in worms overexpressing hsf-1.

A Conformation-Specific Approach to Native Top-down Mass Spectrometry.

Native top-down mass spectrometry is a powerful approach for characterizing proteoforms and has recently been applied to provide similarly powerful insights into protein conformation. Current approaches, however, are limited such that structural insights can only be obtained for the entire conformational landscape in bulk or without any direct conformational measurement. We report a new ion-mobility-enabled method for performing native top-down MS in a conformation-specific manner.