Biophysical characterization of the interaction between FAAP20-UBZ4 domain and Rev1-BRCT domain

FEBS Lett. 2015 Oct 7;589(20 Pt B):3037-43. doi: 10.1016/j.febslet.2015.08.021. Epub 2015 Aug 28.

Abstract

FAAP20 (Fanconi anemia-associated protein 20) is a subunit of the Fanconi anemia (FA) core complex that repairs interstrand cross-links. To understand the molecular basis for the FA core complex-mediated recruitment of Rev1 to the DNA lesion, we characterized the interactions among FAAP20-UBZ4, Rev1-BRCT, and ubiquitin using NMR. We found that FAAP20-UBZ4 binds not only ubiquitin but also Rev1-BRCT. Mapping the protein-protein interactions showed that FAAP20-UBZ4 has distinct binding surfaces for ubiquitin and Rev1-BRCT. In addition, the chemical exchange patterns indicated that the interaction between FAAP20-UBZ4 and ubiquitin might enhance the binding affinity between FAAP20-UBZ4 and Rev1-BRCT. These results provide new insight into the Rev1 recognition mechanism by FAAP20.

Keywords: Fanconi anemia pathway; Fanconi anemia-associated protein 20; Interstrand cross-link; Nuclear magnetic resonance; Rev1; Ubiquitin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites / genetics
  • Biophysical Phenomena
  • Fanconi Anemia Complementation Group Proteins / chemistry*
  • Fanconi Anemia Complementation Group Proteins / genetics
  • Fanconi Anemia Complementation Group Proteins / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nucleotidyltransferases / chemistry*
  • Nucleotidyltransferases / genetics
  • Nucleotidyltransferases / metabolism
  • Protein Binding
  • Protein Interaction Mapping
  • Protein Structure, Tertiary*
  • Sequence Homology, Amino Acid
  • Surface Properties
  • Ubiquitin / chemistry
  • Ubiquitin / metabolism

Substances

  • FAAP20 protein, human
  • Fanconi Anemia Complementation Group Proteins
  • Nuclear Proteins
  • Ubiquitin
  • Nucleotidyltransferases
  • REV1 protein, human