Structure of the ATP-dependent oligomerization domain of N-ethylmaleimide sensitive factor complexed with ATP

  title={Structure of the ATP-dependent oligomerization domain of N-ethylmaleimide sensitive factor complexed with ATP},
  author={Richard C. Yu and Phyllis I Hanson and Reinhard Jahn and Axel T. Br{\"u}nger},
  journal={Nature Structural Biology},
N-ethylmaleimide-sensitive factor (NSF) is a hexameric ATPase which primes and/or dissociates SNARE complexes involved in intracellular fusion events. Each NSF protomer contains three domains: an N-terminal domain required for SNARE binding and two ATPase domains, termed D1 and D2, with D2 being required for oligomerization. We have determined the 1.9 Å crystal structure of the D2 domain of NSF complexed with ATP using multi-wavelength anomalous dispersion phasing. D2 consists of a nucleotide… 
Requirements for the catalytic cycle of the N-ethylmaleimide-Sensitive Factor (NSF).
Crystal structure of the Sec18p N-terminal domain.
  • S. M. Babor, D. Fass
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1999
The structure of the N-terminal domain from Sec18p is determined by x-ray crystallography and all three independent molecules in the crystal asymmetric unit have the identical subdomain interface, supporting the notion that this interface is a preferred packing arrangement.
Dissecting the N-Ethylmaleimide-sensitive Factor
Functional roles for many of the structural elements of the N domain and of the D1 ATP-binding site of NSF are established, and Mutagenesis of Sensor 1, Sensor 2, and Arginine Fingers in NSF-D1 shows that each region plays a discrete role.
Analysis of Nucleotide Binding to P97 Reveals the Properties of a Tandem AAA Hexameric ATPase*S⃞
It is reported that adenosine 5′-O-(thiotriphosphate) (ATPγS) binds with similar affinity to D1 and D2, but ADP binds with higher affinity to L2 than D1, offering an explanation for the higher ATPase activity in D2.
Crystal structure of the amino-terminal domain of N-ethylmaleimide-sensitive fusion protein
Structural-based sequence alignments indicate that in addition to NSF orthologues, the p97 family of ATPases contain an amino-terminal domain of similar structure.
Structural principles of SNARE complex recognition by the AAA+ protein NSF
The recycling of SNARE proteins following complex formation and membrane fusion is an essential process in eukaryotic trafficking. A highly conserved AAA+ protein, NSF (N-ethylmaleimide sensitive
Interplay between an AAA module and an integrin I domain may regulate the function of magnesium chelatase.
In chlorophyll biosynthesis, insertion of Mg(2+) into protoporphyrin IX is catalysed in an ATP-dependent reaction by a three-subunit (BchI, BchD and BchH) enzyme magnesium chelatase, and the three-dimensional structure of the ATP-binding subunit BchI is presented to provide insight into the subunit organisation of magnesiumChelatase and the homologous colbalt chelatases.
Analysis of the AAA sensor-2 motif in the C-terminal ATPase domain of Hsp104 with a site-specific fluorescent probe of nucleotide binding
  • D. Hattendorf, S. Lindquist
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 2002
An R826M mutation causes nearly equal decreases in affinity of NBD2 for both ATP and ADP, indicating that at this site, the sensor-2 provides binding energy, but does not act to sense the difference between these nucleotides.
Crystal Structure of ClpA, an Hsp100 Chaperone and Regulator of ClpAP Protease*
In a planar hexamer model of Cl pA, built by assembling ClpA D1 and D2 into homohexameric rings of known structures of AAA+ modules, the differences in D1-D1 andD2-D2 interfaces correlate with their respective contributions to hexamer stability and ATPase activity.


Each Domain of the N-Ethylmaleimide-sensitive Fusion Protein Contributes to Its Transport Activity (*)
Data demonstrate that NSF binding to the SNAP•SNARE complex is mediated by the N domain and that both ATP binding and hydrolysis by the D1 domain are essential for 20 S particle dynamics.
N-ethylmaleimide-sensitive fusion protein: a trimeric ATPase whose hydrolysis of ATP is required for membrane fusion
It is demonstrated that the ability of the D1 domain to hydrolyze ATP is required for NSF activity and, therefore, required for membrane fusion.
N-Ethylmaleimide-sensitive Fusion Protein Contains High and Low Affinity ATP-binding Sites That Are Functionally Distinct*
Nucleotide concentration greatly affected the ability of NSF to interact with α-SNAP·SNARE (soluble NSF attachment protein- SNAP receptor) complex, suggesting that only when the D1 domain ATP-binding sites are occupied does NSF bind to the α- SNPARE complex.
Role of two nucleotide-binding regions in an N-ethylmaleimide-sensitive factor involved in vesicle-mediated protein transport.
The idea that NSF incorporated into transport vesicles is nonexchangeable for exogenously added NSF is supported, as it was observed in wild-type NSF.
A Revised Model for the Oligomeric State of the N-Ethylmaleimide-sensitive Fusion Protein, NSF*
The demonstration that NSF is a hexameric oligomer highlights structural similarities between it and several related ATPases which act by switching the conformational states of their protein substrates in order to activate them for subsequent reactions.
N-Ethylmaleimide-sensitive Factor Acts at a Prefusion ATP-dependent Step in Ca2+-activated Exocytosis*
NSF-catalyzed activation of SNARE proteins may reorganize membranes to generate a vesicle-plasma membrane prefusion intermediate that is poised for conversion to full fusion by Ca2+-dependent mechanisms.
The 2.4 Å crystal structure of the bacterial chaperonin GroEL complexed with ATPγS
The crystal structure of GroEL with ATPγS bound to each subunit shows that ATP binds to a novel pocket, whose primary sequence is highly conserved among chaperonins.