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Crystal structure of the amino-terminal domain of N-ethylmaleimide-sensitive fusion protein

Nature Cell Biology volume 1, pages 175–182 (1999)Cite this article

Abstract

The cytosolic ATPase N-ethylmaleimide-sensitive fusion protein (NSF) disassembles complexes of membrane-bound proteins known as SNAREs, an activity essential for vesicular trafficking. The amino-terminal domain of NSF (NSF-N) is required for the interaction of NSF with the SNARE complex through the adaptor protein α-SNAP. The crystal structure of NSF-N reveals two subdomains linked by a single stretch of polypeptide. A polar interface between the two subdomains indicates that they can move with respect to one another during the catalytic cycle of NSF. Structure-based sequence alignments indicate that in addition to NSF orthologues, the p97 family of ATPases contain an amino-terminal domain of similar structure.

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Figure 1: Structure of NSF-N.
Figure 2: Structure-based sequence alignment of NSF-N and related domains.
Figure 3: Stucture of the interface between the N- and C-terminal subdomains.
Figure 4: Structure of the NSF-N trimer found in the crystallographic asymmetric unit.

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Acknowledgements

We thank H. Bellamy and N. Sauter for beamline support and assistance during data collection; A. Morgan for communication of unpublished results; and R. Scheller for comments on the manuscript. This work is based upon research conducted at the SSRL, which is funded by the Department of Energy, Office of Basic Energy Sciences. The Biotechnology Program is supported by the NIH, National Center for Research Resources, Biomedical Technology Program and Department of Energy, Office of Biological and Environmental Research. A.P.M. was supported by a Stanford Medical School Dean’s Postdoctoral Fellowship and a Wellcome Trust International Prize Travelling Research Fellowship. K.M.S.M. was supported by Molecular Biophysics Training Grant GM08294 from the NIH. This work was supported by NIH grants HL56652 (to S.W.W.) and MH58570 (to W.I.W.) and by the Pew Scholars Program in the Biomedical Sciences (W.I.W.).

Correspondence and requests for materials should be addressed to W.I.W. Coordinates and structure factors have been deposited in Protein Data Bank under accession code 1QDN.

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  1. Department of Structural Biology, Stanford University School of Medicine, Stanford, 94305, California, USA

    Andrew P. May, Kira M. S. Misura & William I. Weis

  2. Department of Biochemistry, Chandler Medical Center, University of Kentucky College of Medicine, Lexington, 40536,, Kentucky, USA

    Sidney W. Whiteheart

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Correspondence to William I. Weis.

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May, A., Misura, K., Whiteheart, S. et al. Crystal structure of the amino-terminal domain of N-ethylmaleimide-sensitive fusion protein. Nat Cell Biol 1, 175–182 (1999). https://doi.org/10.1038/11097

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