A conserved domain is present in different families of vesicular fusion proteins: a new superfamily.
We have analyzed conserved domains in t-SNAREs [soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptors in the target membrane], proteins that are believed to be involved in the fusion of transport vesicles with their target membrane. By using a sensitive computer method, the generalized profile method, we were able to identify a new homology domain that is common in the two protein families previously identified to act as t-SNAREs, the syntaxin and SNAP-25 (synaptosome-associated protein of 25 kDa) families, which therefore constitute a new superfamily. This homology domain of approximately 60 amino acids is predicted to form a coiled-coil structure. The significance of this homology domain could be demonstrated by a partial suppression of the coiled-coil properties of the domain profile. In proteins belonging to the syntaxin family, a single homology domain is located near the transmembrane domain, whereas the members of the SNAP-25 family possess two homology domains. This domain was also identified in several proteins that have been implicated in vesicular transport but do not belong to any of the t-SNARE protein families. Several new yeast, nematode, and mammalian proteins were identified that belong to the new superfamily. The evolutionary conservation of the SNARE coiled-coil homology domain suggests that this domain has a similar function in different membrane fusion proteins.
Weimbs
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T
Department of Anatomy, University of California, San Francisco 94143-0452, USA. weimbs@itsa.ucsf.edu
Low
S H
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Chapin
S J
SJ
Mostov
K E
KE
Bucher
P
P
Hofmann
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K
D000595:Amino Acid Sequence; D017124:Conserved Sequence; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000502:physiology; D011487:Protein Conformation; D050765:Qa-SNARE Proteins; D017386:Sequence Homology, Amino Acid; D050825:Synaptosomal-Associated Protein 25
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D050825:Synaptosomal-Associated Protein 25