F
IPR000744

NSF attachment protein

InterPro entry
Short nameNSF_attach
Overlapping
homologous
superfamilies
 

Description

Regulated exocytosis of neurotransmitters and hormones, as well as intracellular traffic, requires fusion of two lipid bilayers. SNARE proteins are thought to form a protein bridge, the SNARE complex, between an incoming vesicle and the acceptor compartment. SNARE proteins contribute to the specificity of membrane fusion, implying that the mechanisms by which SNAREs are targeted to subcellular compartments are important for specific docking and fusion of vesicles. This mechanism involves a family of conserved proteins, members of which appear to function at all sites of constitutive and regulated secretion in eukaryotes
[2]
. Among them are 2 types of cytosolic protein, NSF (N-ethyl-maleimide-sensitive protein) and the SNAPs (alpha-, beta- and gamma-soluble NSF attachment proteins). The yeast vesicular fusion protein, sec17, a cytoplasmic peripheral membrane protein involved in vesicular transport between the endoplasmic reticulum and the golgi apparatus, shows a high degree of sequence similarity to the alpha-SNAP family.

Alpha-SNAP is universally present in eukaryotes and acts as an adaptor protein between SNARE (integral membrane SNAP receptor) and NSF for recruitment to the 20S complex. Beta-SNAP is brain-specific and shares high sequence identity (about 85%) with alpha-SNAP. Gamma-SNAP is weakly related (about 20-25% identity) to the two other isoforms, and is ubiquitous. It may help regulate the activity of the 20S complex. The X-ray structures of vertebrate gamma-SNAP and Sec17 show similar all-helical structures consisting of an N-terminal extended twisted sheet of four tetratricopeptide repeat (TPR)-like helical hairpins and a C-terminal helical bundle
[3, 4, 5, 6, 7, 8, 9, 10]
.

SNAP-25 and its non-neuronal homologue Syndet/SNAP-23 are synthesized as soluble proteins in the cytosol. Both SNAP-25 and Syndet/SNAP-23 are palmitoylated at cysteine residues clustered in a loop between two N- and C-terminal coils and palmitoylation is essential for membrane binding and plasma membrane targeting. The C-terminal and the N-terminal helices of SNAP-25, are each targeted to the plasma membrane by two distinct cysteine-rich domains and appear to regulate the availability of SNAP to form complexes with SNARE
[1]
.

References

1.Plasma membrane targeting of SNAP-25 increases its local concentration and is necessary for SNARE complex formation and regulated exocytosis. Koticha DK, McCarthy EE, Baldini G. J. Cell. Sci. 115, 3341-51, (2002). View articlePMID: 12140265

2.A TPR domain in the SNAP secretory proteins. Ordway RW, Pallanck L, Ganetzky B. Trends Biochem. Sci. 19, 530-1, (1994). View articlePMID: 7846761

3.Structure and dynamics of gamma-SNAP: insight into flexibility of proteins from the SNAP family. Bitto E, Bingman CA, Kondrashov DA, McCoy JG, Bannen RM, Wesenberg GE, Phillips GN Jr. Proteins 70, 93-104, (2008). View articlePMID: 17634982

4.Crystal structure of the vesicular transport protein Sec17: implications for SNAP function in SNARE complex disassembly. Rice LM, Brunger AT. Mol. Cell 4, 85-95, (1999). View articlePMID: 10445030

5.A ubiquitous membrane fusion protein alpha SNAP: a potential therapeutic target for cancer, diabetes and neurological disorders? Andreeva AV, Kutuzov MA, Voyno-Yasenetskaya TA. Expert Opin. Ther. Targets 10, 723-33, (2006). View articlePMID: 16981829

6.Cellular functions of NSF: not just SNAPs and SNAREs. Zhao C, Slevin JT, Whiteheart SW. FEBS Lett. 581, 2140-9, (2007). View articlePMID: 17397838

7.Disassembly of all SNARE complexes by N-ethylmaleimide-sensitive factor (NSF) is initiated by a conserved 1:1 interaction between α-soluble NSF attachment protein (SNAP) and SNARE complex. Vivona S, Cipriano DJ, O'Leary S, Li YH, Fenn TD, Brunger AT. J. Biol. Chem. 288, 24984-91, (2013). View articlePMID: 23836889

8.A conserved membrane attachment site in alpha-SNAP facilitates N-ethylmaleimide-sensitive factor (NSF)-driven SNARE complex disassembly. Winter U, Chen X, Fasshauer D. J. Biol. Chem. 284, 31817-26, (2009). View articlePMID: 19762473

9.Defining the SNARE complex binding surface of alpha-SNAP: implications for SNARE complex disassembly. Marz KE, Lauer JM, Hanson PI. J. Biol. Chem. 278, 27000-8, (2003). View articlePMID: 12730228

10.SNAP family of NSF attachment proteins includes a brain-specific isoform. Whiteheart SW, Griff IC, Brunner M, Clary DO, Mayer T, Buhrow SA, Rothman JE. Nature 362, 353-5, (1993). View articlePMID: 8455721

GO terms

molecular function

  • None

cellular component

  • None
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