Chaperoning SNARE Folding and Assembly

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 role...

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Bibliographic Details
Published in:Annual review of biochemistry 2021-06, Vol.90 (1), p.581-603
Main Authors: Zhang, Yongli, Hughson, Frederick M
Format: Article
Language:English
Subjects:
Assembly
Chaperones
Disease - genetics
Exocytosis
Folding
Humans
Membrane Fusion
Membranes
Molecular Chaperones - chemistry
Molecular Chaperones - metabolism
Multiprotein Complexes - chemistry
Multiprotein Complexes - metabolism
Munc18 Proteins - chemistry
Munc18 Proteins - metabolism
Munc18-1
Mutation
Optical Tweezers
Phosphorylation
Protein Domains
Protein Folding
Proteins
SM proteins
SNAP receptors
SNARE assembly
SNARE Proteins - chemistry
SNARE Proteins - genetics
SNARE Proteins - metabolism
template complex
Vesicle fusion
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Summary: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.
ISSN:0066-4154
1545-4509
1545-4509
DOI:10.1146/annurev-biochem-081820-103615