1. The Howard Hughes Medical Institute and Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA
2. Department of Neurobiology, Max-Planck-Institute for Biophysical Chemistry, D-37077 Göttingen, Germany

Correspondence to: Axel T. Brunger¹ Correspondence and requests for materials should be addressed to A.T.B. (e-mail: Email: brunger@laplace.csb.yale.edu). The refined coordinates and diffraction data have been deposited with the Brookhaven Protein Databank, accession number 1sfc. Coordinates are immediately available from http://atb.csb.yale.edu

Abstract

The evolutionarily conserved SNARE proteins and their complexes are involved in the fusion of vesicles with their target membranes; however, the overall organization and structural details of these complexes are unknown. Here we report the X-ray crystal structure at 2.4 Å resolution of a core synaptic fusion complex containing syntaxin-1A, synaptobrevin-II and SNAP-25B. The structure reveals a highly twisted and parallel four-helix bundle that differs from the bundles described for the haemagglutinin and HIV/SIV gp41 membrane-fusion proteins. Conserved leucine-zipper-like layers are found at the centre of the synaptic fusion complex. Embedded within these leucine-zipper layers is an ionic layer consisting of an arginine and three glutamine residues contributed from each of the four -helices. These residues are highly conserved across the entire SNARE family. The regions flanking the leucine-zipper-like layers contain a hydrophobic core similar to that of more general four-helix-bundle proteins. The surface of the synaptic fusion complex is highly grooved and possesses distinct hydrophilic, hydrophobic and charged regions. These characteristics may be important for membrane fusion and for the binding of regulatory factors affecting neurotransmission.

1. The Howard Hughes Medical Institute and Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA
2. Department of Neurobiology, Max-Planck-Institute for Biophysical Chemistry, D-37077 Göttingen, Germany

Correspondence to: Axel T. Brunger¹ Correspondence and requests for materials should be addressed to A.T.B. (e-mail: Email: brunger@laplace.csb.yale.edu). The refined coordinates and diffraction data have been deposited with the Brookhaven Protein Databank, accession number 1sfc. Coordinates are immediately available from http://atb.csb.yale.edu