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Functional architecture of an intracellular membrane t-SNARE

Nature volume 407, pages 198202 (14 September 2000) | Download Citation

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Abstract

Lipid bilayer fusion is mediated by SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) located on the vesicle membrane (v-SNAREs) and the target membrane (t-SNAREs)1,2. The assembled v-SNARE/t-SNARE complex consists of a bundle of four helices, of which one is supplied by the v-SNARE and the other three by the t-SNARE3. For t-SNAREs on the plasma membrane, the protein syntaxin4 supplies one helix and a SNAP-25 protein5 contributes the other two. Although there are numerous homologues of syntaxin on intracellular membranes6, there are only two SNAP-25-related proteins in yeast, Sec9 and Spo20, both of which are localized to the plasma membrane and function in secretion7 and sporulation8, respectively. What replaces SNAP-25 in t-SNAREs of intracellular membranes? Here we show that an intracellular t-SNARE is built from a ‘heavy chain’ homologous to syntaxin and two separate non-syntaxin ‘light chains’. SNAP-25 may thus be the exception rather than the rule, having been derived from genes that encoded separate light chains that fused during evolution to produce a single gene encoding one protein with two helices.

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Acknowledgements

We wish to thank B. Brügger for preparation of the vacuolar lipid mixture and T. Wolfe for help with the manuscript. This work was supported by an NIH grant (to J.E.R.) and postdoctoral fellowships of the Japan Society for the Promotion of Science (to R.F.), the Human Frontiers Science Program Organization (to W.N.), the Deutsche Forschungsgemeinschaft (to T.E.), the Medical Research Council of Canada (to F.P.), the National Institutes of Health (to J.A.M.), the Swiss National Science Foundation (to T.W.) and the European Molecular Biology Organization (to T.W.).

Author information

Author notes

    • Ryouichi Fukuda
    • , James A. McNew
    • , Thomas Weber
    • , Thomas Engel
    •  & Walter Nickel

    Present addresses: Department of Biotechnology, The University of Tokyo, 1-1-1, Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan (R.F); Department of Biochemistry and Cell Biology, Rice University, MS140, 6100 Main Street, PO Box 1892, Houston, Texas 77251-1892, USA (J.A.M.); Institute for Gene Therapy and Molecular Medicine, Box 1496, Mount Sinai School of Medicine, 1425 Madison Avenue, New York, New York 10029-6574, USA (T.W.); Institut für Arterioskleroseforschung an der Westfälischen Wilhelms-Universität, Domagkstraße 3, D-48149 Münster, Germany (T.E.); Biochemie-Zentrum Heidelberg, Ruprecht-Karls-Universität , Im Neuenheimer Feld 328, D-69120 Heidelberg, Germany (W.N.).

Affiliations

  1. Cellular Biochemistry & Biophysics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 519, New York, New York 10021, USA

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https://doi.org/10.1038/35025084

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