1urq | pdb_00001urq
Crystal structure of neuronal Q-SNAREs in complex with R-SNARE motif of Tomosyn
Structural highlights
FunctionSTXB5_RAT Inhibits translocation of GLUT4 from intracellular vesicles to the plasma membrane (By similarity). Plays a regulatory role in calcium-dependent exocytosis and neurotransmitter release. Inhibits membrane fusion between transport vesicles and the plasma membrane. May modulate the assembly of trans-SNARE complexes between transport vesicles and the plasma membrane. Competes with STXBP1 for STX1 binding.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedUpon Ca2+ influx synaptic vesicles fuse with the plasma membrane and release their neurotransmitter cargo into the synaptic cleft. Key players during this process are the Q-SNAREs syntaxin 1a and SNAP-25 and the R-SNARE synaptobrevin 2. It is thought that these membrane proteins gradually assemble into a tight trans-SNARE complex between vesicular and plasma membrane, ultimately leading to membrane fusion. Tomosyn is a soluble protein of 130 kDa that contains a COOH-terminal R-SNARE motif but lacks a transmembrane anchor. Its R-SNARE motif forms a stable core SNARE complex with syntaxin 1a and SNAP-25. Here we present the crystal structure of this core tomosyn SNARE complex at 2.0-A resolution. It consists of a four-helical bundle very similar to that of the SNARE complex containing synaptobrevin. Most differences are found on the surface, where they prevented tight binding of complexin. Both complexes form with similar rates as assessed by CD spectroscopy. In addition, synaptobrevin cannot displace the tomosyn helix from the tight complex and vice versa, indicating that both SNARE complexes represent end products. Moreover, data bank searches revealed that the R-SNARE motif of tomosyn is highly conserved throughout all eukaryotic kingdoms. This suggests that the formation of a tight SNARE complex is important for the function of tomosyn. Structural basis for the inhibitory role of tomosyn in exocytosis.,Pobbati AV, Razeto A, Boddener M, Becker S, Fasshauer D J Biol Chem. 2004 Nov 5;279(45):47192-200. Epub 2004 Aug 16. PMID:15316007[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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