Multiple binding proteins suggest diverse functions for the N-ethylmaleimide sensitive factor

Sidney W. Whiteheart, Elena A. Matveeva

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


The hexameric ATPase, N-ethylmaleimide sensitive factor (NSF), is essential to vesicular transport and membrane fusion because it affects the conformations and associations of the soluble NSF attachment protein receptor (SNARE) proteins. NSF binds SNAREs through adaptors called soluble NSF attachment proteins (α- or β-SNAP) and disassembles SNARE complexes to recycle the monomers. NSF contains three domains, two nucleotide-binding domains (NSF-D1 and -D2) and an amino terminal domain (NSF-N) that is required for SNAP-SNARE complex binding. Mutagenesis studies indicate that a cleft between the two sub-domains of NSF-N is critical for binding. The structural conservation of N domains in NSF, p97/VCP, and VAT suggests that a similar type of binding site could mediate substrate recognition by other AAA proteins. In addition to SNAP-SNARE complexes, NSF also binds other proteins and protein complexes such as AMPA receptor subunits (GluR2), β2-adrenergic receptor, β-Arrestin1, GATE-16, LMA1, rabs, and rab-containing complexes. The potential for these interactions indicates a broader role for NSF in the assembly/disassembly cycles of several cellular complexes and suggests that NSF may have specific regulatory effects on the functions of the proteins involved in these complexes. The structural requirements for these interactions and their physiological significance will be discussed.

Original languageEnglish
Pages (from-to)32-43
Number of pages12
JournalJournal of Structural Biology
Issue number1-2
StatePublished - Apr 2004

Bibliographical note

Funding Information:
The authors thank Tara Rutledge, Todd Schraw, Garland Crawford, Wangsun Choi, and Qiansheng (Jason) Ren, for their discussions and critical reading of the manuscript. We would especially like to thank Byron DeLaBarre for his comments and corrections to this manuscript. We also thank Todd Schraw for his contribution to Fig. 3 . This work is supported by a grant from the National Institutes of Health, HL56652.


  • AMPA receptor (GluR2)
  • Arrestin
  • GATE-16
  • N-Ethylmaleimide sensitive factor
  • Rab
  • SNAP receptor
  • Soluble NSF attachment protein
  • β2-adrenergic receptor

ASJC Scopus subject areas

  • Structural Biology


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