A Conserved Domain is Present in Different Families of Vesicular Fusion Proteins: A New Superfamily

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 94; no. 7; pp. 3046 - 3051
• Main Authors: Weimbs, Thomas, Low, Seng Hui, Chapin, Steven J., Mostov, Keith E., Bucher, Philipp, Hofmann, Kay
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 01.04.1997; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences of the USA
• Subjects: Amino Acid Sequence; Amino acids; Biological Sciences; Cell membranes; Cellular biology; Conserved Sequence; Mathematical functions; Membrane Fusion; Membrane Proteins - chemistry; Membranes; Molecular Sequence Data; Nematodes; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - physiology; P branes; Protein Conformation; Protein isoforms; Proteins; Qa-SNARE Proteins; Sequence Homology, Amino Acid; SNARE proteins; Synaptosomal-Associated Protein 25; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.7.3046

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.