3QQ7

Crystal Structure of the p97 N-terminal domain

Summary for 3QQ7

• Entry DOI: 10.2210/pdb3qq7/pdb
• Descriptor: Transitional endoplasmic reticulum ATPase, HEXANE-1,6-DIOL, GLYCEROL, ... (6 entities in total)
• Functional Keywords: beta-barrel, atpase, ubiquitin, phosphorylation, transport protein
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytosol : P55072
• Total number of polymer chains: 1
• Total formula weight: 21208.71

Authors

Haenzelmann, P.,Schindelin, H. (deposition date: 2011-02-15, release date: 2011-06-22, Last modification date: 2024-02-21)

Primary citation

Hanzelmann, P.,Buchberger, A.,Schindelin, H.
Hierarchical Binding of Cofactors to the AAA ATPase p97.
Structure, 19:833-843, 2011

PubMed Abstract: The hexameric AAA ATPase p97 is involved in several human proteinopathies and mediates ubiquitin-dependent protein degradation among other essential cellular processes. Via its N-terminal domain (N domain), p97 interacts with multiple regulatory cofactors including the UFD1/NPL4 heterodimer and members of the "ubiquitin regulatory X" (UBX) domain protein family; however, the principles governing cofactor selectivity remain to be deciphered. Our crystal structure of the FAS-associated factor 1 (FAF1)UBX domain in complex with the p97N domain reveals that the signature Phe-Pro-Arg motif known to be crucial for interactions of UBX domains with p97 adopts a cis-proline configuration, in contrast to a cis-trans mixture we derive for the isolated FAF1UBX domain. Biochemical studies confirm that binding critically depends on a proline at this position. Furthermore, we observe that the UBX proteins FAF1 and UBXD7 only bind to p97-UFD1/NPL4, but not free p97, thus demonstrating for the first time a hierarchy in p97-cofactor interactions.

PubMed: 21645854
DOI: 10.1016/j.str.2011.03.018

Experimental method

X-RAY DIFFRACTION (2.65 Å)