Volume 29 Issue 10, October 2022

Recent structures of the three-way complex formed by the scaffold protein SHOC2, the small G protein M-RAS and protein phosphatase 1 (PP1) provide a tantalizing insight into the activation of RAF, the oncogenic kinase and downstream effector of RAS that drives cell proliferation and survival.

A cryo-EM structure of disease-related human Y145Stop prion protein amyloid fibrils explains species-dependent seeding barriers in prion protein amyloid propagation.

The high-resolution crystal structure of the SHOC2–MRAS–PP1C complex provides insights into the complex assembly, RAF dephosphorylation, MRAS selectivity versus canonical RAS isoforms, and the impact of Noonan syndrome mutations on complex formation.

This study identifies protein structural changes in cerebrospinal fluid of people with Parkinson’s disease relative to healthy individuals and proposes the concept of structural disease biomarkers. It also analyzes proteome structural variability in healthy people.

Happ et al. uncover an unusual regulatory mechanism in the Hedgehog signaling pathway, which enables a G protein-coupled receptor to physically block the enzymatic activity of a major cellular kinase.

Here, Dimitrova et al. examine how CKM–Mediator and Polycomb shape 3D chromosome interactions in ESCs and discover that gene activation during differentiation is independent of pre-formed interactions but depends on recruitment of the core Mediator.

The authors present Modeling immuno-OligoSTORM (MiOS), a super-resolution imaging and computational strategy to model 3D gene folding at multiple genomic scales, reaching nucleosome resolution at the single-gene level.

The tumor suppressor ARF is retained by nucleophosmin (NPM) in nucleoli, but shifted out upon DNA damage. In this study, the authors show that cytochrome c triggers a conformational change on NPM, driving ARF release and controlling protein trafficking.