Crystal structures of the UBX domain of human UBXD7 and its complex with p97 ATPase

Zhi-Hui Li; Yong Wang; Min Xu; Tao Jiang

doi:10.1016/j.bbrc.2017.03.005

Crystal structures of the UBX domain of human UBXD7 and its complex with p97 ATPase

Biochem Biophys Res Commun. 2017 Apr 22;486(1):94-100. doi: 10.1016/j.bbrc.2017.03.005. Epub 2017 Mar 6.

Authors

Zhi-Hui Li¹, Yong Wang¹, Min Xu¹, Tao Jiang²

Affiliations

¹ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, 19A Yuquan Road, Shijingshan District, Beijing 100049, China.
² National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, 19A Yuquan Road, Shijingshan District, Beijing 100049, China. Electronic address: tjiang@ibp.ac.cn.

PMID: 28274878
DOI: 10.1016/j.bbrc.2017.03.005

Abstract

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 p97 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 (UBXD7^UBX) at 2.0 Å resolution and its complex with p97 N-terminal domain (p97^NTD-UBXD7^UBX complex) at 2.4 Å resolution. A structural analysis and isothermal titration calorimetry results provide detailed molecular basis of interaction between UBXD7^UBX and p97^NTD. Moreover, structural superpositions suggest that dimerization of UBXD7^UBX via an intermolecular disulfide bond could interfere with the formation of the p97^NTD-UBXD7^UBX complex. Interestingly, UBXD7 may have a cooperative effect on p97 interaction with UFD1. Together, these results provide structural and biochemical insights into the interaction between p97^NTD and UBXD7^UBX.

Keywords: Crystal structure; SHP box; UBXD7(UBX); UPS; p97(NTD).

MeSH terms

Adaptor Proteins, Signal Transducing
Adenosine Triphosphatases / chemistry*
Adenosine Triphosphatases / genetics
Adenosine Triphosphatases / metabolism
Amino Acid Sequence
Binding Sites / genetics
Calorimetry / methods
Carrier Proteins / chemistry*
Carrier Proteins / genetics
Carrier Proteins / metabolism
Crystallization
Crystallography, X-Ray
Disulfides / chemistry
Humans
Models, Molecular
Mutation
Nuclear Proteins / chemistry*
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Protein Binding
Protein Domains*
Protein Multimerization
Sequence Homology, Amino Acid

Substances

Adaptor Proteins, Signal Transducing
Carrier Proteins
Disulfides
Nuclear Proteins
UBXN7 protein, human
Adenosine Triphosphatases
p97 ATPase