Crystal structures of the UBX domain of human UBXD7 and its complex with p97 ATPase.
In humans, UBXD7 (also called UBXN7), an adaptor of p97 ATPase, can participate in the degradation of misfolded or damaged proteins in the p97-mediated ubiquitin proteasome system (UPS). UBXD7 binds to ubiquitinated substrates via its UBA domain and interacts with p97Â N-terminal domain through its UBX domain to recruit p97 or ... the p97 core complex (p97/NPL4/UFD1). Here, we report the crystal structures of the UBX domain of UBXD7 (UBXD7UBX) at 2.0Â A resolution and its complex with p97Â N-terminal domain (p97NTD-UBXD7UBXcomplex) at 2.4Â A resolution. A structural analysis and isothermal titration calorimetry results provide detailed molecular basis of interaction between UBXD7UBXand p97NTD. Moreover, structural superpositions suggest that dimerization of UBXD7UBXvia an intermolecular disulfide bond could interfere with the formation of the p97NTD-UBXD7UBXcomplex. Interestingly, UBXD7 may have a cooperative effect on p97 interaction with UFD1. Together, these results provide structural and biochemical insights into the interaction between p97NTDand UBXD7UBX.
Mesh Terms:
Adenosine Triphosphatases, Amino Acid Sequence, Binding Sites, Calorimetry, Carrier Proteins, Crystallization, Crystallography, X-Ray, Disulfides, Humans, Models, Molecular, Mutation, Nuclear Proteins, Protein Binding, Protein Domains, Protein Multimerization, Sequence Homology, Amino Acid
Adenosine Triphosphatases, Amino Acid Sequence, Binding Sites, Calorimetry, Carrier Proteins, Crystallization, Crystallography, X-Ray, Disulfides, Humans, Models, Molecular, Mutation, Nuclear Proteins, Protein Binding, Protein Domains, Protein Multimerization, Sequence Homology, Amino Acid
Biochem. Biophys. Res. Commun.
Date: Dec. 22, 2016
PubMed ID: 28274878
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