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-ethylmaleimi de-sensitive factor (NSF) attachment protein (SNAP) receptors in the t arget membrane], proteins that are believed to be involved in the fusi on of transport vesicles with their target membrane, By using a sensit ive computer method, the generalized profile method, we were able to i dentify a new homology domain that is common in the two protein famili es previously identified to act as t-SNAREs, the syntaxin and SNAP-25 (synaptosome-associated protein of 25 kDa) families, which therefore c onstitute a new superfamily. This homology domain of approximately 60 amino acids is predicted to form a coiled-coil structure. The signific ance of this homology domain could be demonstrated by a pal tial suppr ession of the coiled-coil properties of the domain profile, In protein s belonging to the syntaxin family, a single homology domain is locate d near the transmembrane domain, whereas the members of the SNAP-25 fa mily 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 yeas t, nematode and mammalian proteins were identified that belong to the new superfamily, The evolutionary conservation of the SNARE coiled-coi l homology domain suggests that this domain has a similar function in different membrane fusion proteins.