Conformational changes in the AAA ATPase p97-p47 adaptor complex.
The AAA+ATPase p97/VCP, helped by adaptor proteins, exerts its essential role in cellular events such as endoplasmic reticulum-associated protein degradation or the reassembly of Golgi, ER and the nuclear envelope after mitosis. Here, we report the three-dimensional cryo-electron microscopy structures at approximately 20 Angstroms resolution in two nucleotide states of the endogenous hexameric p97 in complex with a recombinant p47 trimer, one of the major p97 adaptor proteins involved in membrane fusion. Depending on the nucleotide state, we observe the p47 trimer to be in two distinct arrangements on top of the p97 hexamer. By combining the EM data with NMR and other biophysical measurements, we propose a model of ATP-dependent p97(N) domain motions that lead to a rearrangement of p47 domains, which could result in the disassembly of target protein complexes.
Beuron
Fabienne
F
Centre for Structural Biology, Division of Molecular Biosciences, Imperial College London, South Kensington, UK.
Dreveny
Ingrid
I
Yuan
Xuemei
X
Pye
Valerie E
VE
McKeown
Ciaran
C
Briggs
Louise C
LC
Cliff
Matthew J
MJ
Kaneko
Yayoi
Y
Wallis
Russell
R
Isaacson
Rivka L
RL
Ladbury
John E
JE
Matthews
Steve J
SJ
Kondo
Hisao
H
Zhang
Xiaodong
X
Freemont
Paul S
PS
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000648:ultrastructure*; D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D020285:Cryoelectron Microscopy; D008958:Models, Molecular; D052066:N-Ethylmaleimide-Sensitive Proteins / Q000737:chemistry / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000737:chemistry / Q000648:ultrastructure*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D050600:SNARE Proteins / Q000737:chemistry; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins / Q000737:chemistry / Q000648:ultrastructure*
D009687:Nuclear Proteins; D050600:SNARE Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; C404942:p97 ATPase; D052066:N-Ethylmaleimide-Sensitive Proteins