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Munc18-1 binds directly to the neuronal SNARE complex
被引:246
作者:
Dulubova, Irina
Khvotchev, Mikhail
Liu, Siqi
Huryeva, Iryna
Sudhof, Thomas C.
Rizo, Josep
机构:
[1] Univ Texas, SW Med Ctr, Dept Biochem & Pharmacol, Dallas, TX 75390 USA
[2] Univ Texas, SW Med Ctr, Dept Neurosci & Mol Genet, Dallas, TX 75390 USA
[3] Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75390 USA
来源:
关键词:
exocytosis;
membrane fusion;
neurotransmitter release;
Sec1/Munc18-like proteins;
synapse;
D O I:
10.1073/pnas.0611318104
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
Both SM proteins (for Sec1/Munc18-like proteins) and SNARE proteins (for soluble NSF-attachment protein receptors) are essential for intracellular membrane fusion, but the general mechanism of coupling between their functions is unclear, in part because diverse SM protein/SNARE binding modes have been described. During synaptic vesicle exocytosis, the SM protein Munc18-1 is known to bind tightly to the SNARE protein syntaxin-1, but only when syntaxin-1 is in a closed conformation that is incompatible with SNARE complex formation. We now show that Munc18-1 also binds tightly to assembled SNARE complexes containing syntaxin-1. The newly discovered Munc18-1/SNARE complex interaction involves contacts of Munc18-1 with the N-terminal H-abc domain of syntaxin-1 and the four-helical bundle of the assembled SNARE complex. Together with earlier studies, our results suggest that binding of Munc18-1 to closed syntaxin-1 is a specialization that evolved to meet the strict regulatory requirements of neuronal exocytosis, whereas binding of Munc18-1 to assembled SNARE complexes reflects a general function of SM proteins involved in executing membrane fusion.
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页码:2697 / 2702
页数:6
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