Chaperoning SNARE Folding and Assembly.

TitleChaperoning SNARE Folding and Assembly.
Publication TypeJournal Article
Year of Publication2021
AuthorsZhang, Y, Hughson, FM
JournalAnnu Rev Biochem
Date Published2021 Jun 20
KeywordsDisease, Humans, Membrane Fusion, Molecular Chaperones, Multiprotein Complexes, Munc18 Proteins, Mutation, Optical Tweezers, Phosphorylation, Protein Domains, Protein Folding, SNARE Proteins

<p>SNARE proteins and Sec1/Munc18 (SM) proteins constitute the core molecular engine that drives nearly all intracellular membrane fusion and exocytosis. While SNAREs are known to couple their folding and assembly to membrane fusion, the physiological pathways of SNARE assembly and the mechanistic roles of SM proteins have long been enigmatic. Here, we review recent advances in understanding the SNARE-SM fusion machinery with an emphasis on biochemical and biophysical studies of proteins that mediate synaptic vesicle fusion. We begin by discussing the energetics, pathways, and kinetics of SNARE folding and assembly in vitro. Then, we describe diverse interactions between SM and SNARE proteins and their potential impact on SNARE assembly in vivo. Recent work provides strong support for the idea that SM proteins function as chaperones, their essential role being to enable fast, accurate SNARE assembly. Finally, we review the evidence that SM proteins collaborate with other SNARE chaperones, especially Munc13-1, and briefly discuss some roles of SNARE and SM protein deficiencies in human disease.</p>

Alternate JournalAnnu Rev Biochem
PubMed ID33823650
PubMed Central IDPMC8900292
Grant ListR01 GM071574 / GM / NIGMS NIH HHS / United States
R35 GM131714 / GM / NIGMS NIH HHS / United States