title: Crystal structures of the UBX domain of human UBXD7 and its complex with p97 ATPase.
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 (UBXD7UBX) at 2.0 Å resolution and its complex with p97 N-terminal domain (p97NTD-UBXD7UBXcomplex) at 2.4 Å 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.
authors.affiliation: 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.
authors.forename: Zhi-Hui
authors.initials: ZH
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000251:Adenosine Triphosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D002151:Calorimetry / Q000379:methods; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003460:Crystallization; D018360:Crystallography, X-Ray; D004220:Disulfides / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D000072417:Protein Domains; D055503:Protein Multimerization; D017386:Sequence Homology, Amino Acid
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D004220:Disulfides; D009687:Nuclear Proteins; C531895:UBXN7 protein, human; D000251:Adenosine Triphosphatases; C404942:p97 ATPase
keywords: Crystal structure; SHP box; UBXD7(UBX); UPS; p97(NTD)