A conserved domain is present in different families of vesicular fusion proteins: A new superfamily

A conserved domain is present in different families of vesicular fusion proteins: A new superfamily

^*Department of Anatomy, Department of Biochemistry and Biophysics, and Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0452; and ^‡Bioinformatics Group, Swiss Institute for Experimental Cancer Research, CH-1066 Epalinges, Switzerland

Abstract

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.

Footnotes

↵ † To whom reprint requests should be addressed at: Department of Anatomy, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA, 94143-0452. e-mail: weimbs{at}itsa.ucsf.edu.
Richard J. Havel, University of California School of Medicine, San Francisco, CA
ABBREVIATIONS:

EST,

expressed sequence tag;

NSF,

N-ethylmaleimide-sensitive factor;

SNAP-25,

synaptosome-associated protein of 25 kDa;

SNAP,

soluble NSF attachment protein;

SNARE,

SNAP receptor;

TSL,

t-SNARE-like;

t-SNARE,

SNARE in the target membrane;

v-SNARE,

SNARE in the vesicle membrane