Volume 28 Issue 10, October 2021

The critical event in KRAS signaling and oncogenic transformation is activation of the RAF–MEK–MAPK cascade. This requires assembly of a multiprotein–lipid complex on the plasma membrane. In a tour de force of modeling, Mysore et al. now provide the first glimpse of what this structure may actually look like.

CTCF is a conserved DNA- and RNA-binding protein with roles in genome folding and transcriptional regulation. Two recent studies investigated how CTCF knockout perturbs genome biology and derails embryogenesis in zebrafish and Drosophila melanogaster, revealing contrasting effects across species.

A series of cryo-EM structures examining transcription initiation by vaccinia poxvirus RNA polymerase reveal how viral transcription factors identify and melt a promoter and how a polymerase-associated helicase mediates promoter escape.

High-resolution cryo-EM structures of human ATM bound to ATPγS and two distinct ATM inhibitors provide insights into the mechanism of inhibitor selectivity and offer a framework for structure-based drug design.

Outer-arm dyneins (OADs) assemble in large arrays on the ciliary axoneme to drive rhythmic beating. Cryo-EM structures of microtubule-bound Tetrahymena thermophila OAD arrays reveal details of this complex assembly and suggest a model for its mechanism of coordinated action.

Here the authors find that Polycomb repressive complex PRC1 functions independently of PRC2 to counteract Pol II binding, regulating transcription initiation and burst frequency.

Cryo-EM and X-ray crystal structures reveal the architecture of the human Xkr8–Basigin complex, providing insights into the molecular mechanism of phospholipid scrambling.

Structures of the dephosphorylation complex for phosphorylated eIF2α reveal how contacts with the regulatory PPP1R15A subunit mediate substrate selectivity, providing a paradigm for dephosphorylation reactions by diverse combinatorially assembled holophosphatases.

A structural model of a K-Ras nanocluster that promotes the stability and accessibility of active K-Ras and creates composite interfaces that facilitate Raf binding provides a framework to unravel MAPK signaling.

PTEN is a key cell signaling lipid phosphatase that is regulated by C-terminal phosphorylation. Biophysical methods were used to illuminate the structural basis for PTEN regulation, which involves a dynamic N-terminal helix that influences catalysis.