Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1823, Issue 1, Pages 159-171Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2011.06.003
Keywords
NSF; Membrane trafficking; ATPase; SNAP; SNARE
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Funding
- NHLBI NIH HHS [R01 HL056652] Funding Source: Medline
- NINDS NIH HHS [R01 NS046242] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL056652] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS046242] Funding Source: NIH RePORTER
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The N-ethylmaleimide-Sensitive Factor (NSF) was one of the initial members of the ATPases Associated with various cellular Activities Plus (AAA(+)) family. In this review, we discuss what is known about the mechanism of NSF action and how that relates to the mechanisms of other AAA(+) proteins. Like other family members, NSF binds to a protein complex (i.e., SNAP-SNARE complex) and utilizes ATP hydrolysis to affect the conformations of that complex. SNAP-SNARE complex disassembly is essential for SNARE recycling and sustained membrane trafficking. NSF is a homo-hexamer; each protomer is composed of an N-terminal domain, NSF-N, and two adjacent AAA-domains. NSF-D1 and NSF-D2. Mutagenesis analysis has established specific roles for many of the structural elements of NSF-D1, the catalytic ATPase domain, and NSF-N, the SNAP-SNARE binding domain. Hydrodynamic analysis of NSF, labeled with (Ni2+-NTA)(2)-Cy3, detected conformational differences in NSF, in which the ATP-bound conformation appears more compact than the ADP-bound form. This indicates that NSF undergoes significant conformational changes as it progresses through its ATP-hydrolysis cycle. Incorporating these data, we propose a sequential mechanism by which NSF uses NSF-N and NSF-D1 to disassemble SNAP-SNARE complexes. We also illustrate how analytical centrifugation might be used to study other AAA(+) proteins. This article is part of a Special Issue entitled: AAA ATPases: structure and function. (C) 2011 Elsevier B.V. All rights reserved.
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