Distinct conformations of the protein complex p97-Ufd1-Npl4 revealed by electron cryomicroscopy.
p97 is a key regulator of numerous cellular pathways and associates with ubiquitin-binding adaptors to remodel ubiquitin-modified substrate proteins. How adaptor binding to p97 is coordinated and how adaptors contribute to substrate remodeling is unclear. Here we present the 3D electron cryomicroscopy reconstructions of the major Ufd1-Npl4 adaptor in complex with p97. Our reconstructions show that p97-Ufd1-Npl4 is highly dynamic and that Ufd1-Npl4 assumes distinct positions relative to the p97 ring upon addition of nucleotide. Our results suggest a model for substrate remodeling by p97 and also explains how p97-Ufd1-Npl4 could form other complexes in a hierarchical model of p97-cofactor assembly.
Centre for Structural Biology and Centre for Biomolecular Electron Microscopy, Division of Molecular Biosciences, Imperial College London, London SW7 2AZ, United Kingdom.
Cecilia
C
Bebeacua
Andreas
A
Förster
Ciarán
C
McKeown
Hemmo H
HH
Meyer
Xiaodong
X
Zhang
Paul S
PS
Freemont
D000251:Adenosine Triphosphatases / Q000648:ultrastructure*; D002352:Carrier Proteins / Q000648:ultrastructure*; D018797:Cell Cycle Proteins / Q000648:ultrastructure*; D020285:Cryoelectron Microscopy / Q000379:methods; D004926:Escherichia coli; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000648:ultrastructure*; D011487:Protein Conformation; D011506:Proteins / Q000648:ultrastructure*; D000074405:Valosin Containing Protein
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; C495985:Nploc4 protein, rat; D011506:Proteins; C107396:Ufd1 protein, mouse; D000251:Adenosine Triphosphatases; D000074405:Valosin Containing Protein