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Three-dimensional structure of the neuronal-Sec1–syntaxin 1a complex

Nature volume 404, pages 355–362 (2000)Cite this article

Abstract

Syntaxin 1a and neuronal Sec1 (nSec1) form an evolutionarily conserved heterodimer that is essential for vesicle trafficking and membrane fusion. The crystal structure of the nSec1–syntaxin 1a complex, determined at 2.6 Å resolution, reveals that major conformational rearrangements occur in syntaxin relative to both the core SNARE complex and isolated syntaxin. We identify regions of the two proteins that seem to determine the binding specificity of particular Sec1 proteins for syntaxin isoforms, which is likely to be important for the fidelity of membrane trafficking. The structure also indicates mechanisms that might couple the action of upstream effector proteins to conformational changes in syntaxin 1a and nSec1 that lead to core complex formation and membrane fusion.

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Figure 1: Structure of nSec1 and syntaxin 1a.
Figure 2: Ribbon representation of the nSec1–syntaxin 1a complex.
Figure 3: Structure-based sequence alignments.
Figure 4: Electrostatic surface potentials of nSec1 and syntaxin 1a.
Figure 5: Sites of Sec1 and syntaxin mutations.
Figure 6: Model for the role of nSec1 in membrane fusion.

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Acknowledgements

We thank H. Bellamy, P. Kuhn, A. Cohen and M. Soltis of SSRL for beamline support; A. Kolatkar, J. Wedekind and members of the Weis laboratory for assistance with data collection and discussions; K. Ervin, R. Hollomon and L. Cai for technical support; F. Hughson for providing Habc coordinates before publication; K. Harlos for providing flat bottom micro-bridges; and A. Brünger, A. May and S. Scales for comments on the manuscript. This work is based on research conducted at SSRL, which is funded by the Department of Energy, Office of Basic Energy Sciences. The Biotechnology Program is supported by the National Institutes of Health, National Center for Research Resources, Biomedical Technology Program and the Department of Energy, Office of Biological and Environmental Research. K.M.S.M was supported by a Molecular Biophysics training grant from the NIH. This work was supported by grants from the National Institutes of Mental Health to R.H.S. and W.I.W., and also the Pew Scholars Program in the Biomedical Sciences and a Stanford University/Howard Hughes Medical Institute Junior Faculty Award to W.I.W.

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Authors and Affiliations

  1. Department of Structural Biology Fairchild Building, Stanford University School of Medicine, 299 Campus Drive West, Stanford, 94305, California, USA

    Kira M. S. Misura & William I. Weis

  2. Molecular and Cellular Physiology and the Howard Hughes Medical Institute, Stanford University School of Medicine , Stanford, 94305, California, USA

    Richard H. Scheller

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  1. Kira M. S. Misura
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Correspondence to William I. Weis.

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Misura, K., Scheller, R. & Weis, W. Three-dimensional structure of the neuronal-Sec1–syntaxin 1a complex . Nature 404, 355–362 (2000). https://doi.org/10.1038/35006120

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