Insights into adaptor binding to the AAA protein p97.
The AAA (ATPase associated with various cellular activities) p97 [also known as VCP (valosin-containing protein)] participates in numerous biological activities and is an essential component of the ubiquitin signalling pathway. A plethora of adaptors have been reported for p97, and increasing evidence is suggesting that it is through adaptor binding that p97 is diverted into different cellular pathways. Studying the interaction between p97 and its adaptors is therefore crucial to our understanding of the physiological roles of the protein. The interactions between p97 and the PUB [PNGase (peptide N-glycosidase)/ubiquitin-associated] domain of PNGase, the UBX (ubiquitin regulatory X) domain of p47, and the UBD (ubiquitin D) domain of Npl4 have been structurally characterized. UBX and UBD are structural homologues that share similar p97-binding modes; it is plausible that other proteins that contain a UBX/UBX-like domain also interact with p97 via similar mechanisms. In addition, several short p97-interacting motifs, such as VBM (VCP-binding motif), VIM (VCP-interacting motif) and SHP, have been identified recently and are also shared between p97 adaptors, hinting that proteins possessing the same p97-binding motif might also share common p97-binding mechanisms. In this review, we aim to summarize our current knowledge on adaptor binding to p97.
Yeung
Heidi O
HO
Division of Molecular Biosciences, Centre for Structural Biology, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, U.K.
Kloppsteck
Patrik
P
Niwa
Hajime
H
Isaacson
Rivka L
RL
Matthews
Steve
S
Zhang
Xiaodong
X
Freemont
Paul S
PS
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008666:Metalloendopeptidases / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000074405:Valosin Containing Protein
D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D008666:Metalloendopeptidases; C114583:m-AAA proteases; D000251:Adenosine Triphosphatases; C000614178:VCP protein, human; D000074405:Valosin Containing Protein