Volume 28 Issue 7, July 2021

The autophagy protein Atg8 regulates autophagosome biogenesis and mediates cargo recruitment in different types of selective autophagy, but the molecular mechanisms mediating Atg8 functions during autophagosome biogenesis have been unclear. A study published in Nature Structural & Molecular Biology now shows that lipidated Atg8 possesses physicochemical activity that regulates membrane morphology, which underlies efficient autophagosome biogenesis.

A new cryo-EM study reveals how ATP hydrolysis in the p97 ATPase is coordinated to unfold the protein’s substrates and provides new foundations for the design of small molecule therapeutics targeting p97 in cancer, neurodegeneration and viral infection.

After years of only low-resolution and partial assemblies, the entire human preinitiation complex (PIC), including the large and flexible Mediator and TFIID complexes, has come into focus. Five recent papers from three different research groups have transformed our understanding of transcription initiation by RNA polymerase II.

A spectrum of high-risk leukemias is caused by recurrent chromosomal translocations that result in the expression of fusion proteins. In a recent article in Nature, it has been demonstrated that the oncogenic properties of one such fusion, NUP98–HOXA9, are linked to its ability to self-associate and function through aberrantly phase-separated “onco-condensates.”

Multiple cryo-EM structures of rat TRPV1 at different temperatures illustrate steps in the heat-dependent gating of this important sensory receptor.

Cryo-EM structures of the heat-activated TRP channel TRPV3 in lipid nanodiscs at different temperatures reveal a conformational wave involved in the gating process.

A cryo-EM structure of SARS-CoV-2 ORF3a reveals a new fold conserved in coronaviruses, and functional experiments show ion channel activity that may be important for viral infectivity.

Lipidated Atg8 affects membrane morphology via two aromatic membrane-facing residues that are important for autophagy in budding yeast and mammalian cells.

The canonical DNA methylation maintenance enzyme Dnmt1 displays global de novo methylation activity with greater targeting towards IAP transposons, which may contribute to their stable repression during early development.

Cryo-EM structures of zebrafish TRPM5 reveal closed and Ca²⁺-bound open states, a unique Ca²⁺ binding site that modulates voltage sensitivity and the mechanism of antagonist action.

A series of high-resolution cryo-EM structures of substrate-engaged human p97 AAA ATPase reveal critical conformational changes of the intersubunit signaling motifs, which contribute to the spiral staircase conformation of the D1 and D2 rings of p97.