Open AccessDNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a
Author(s) -
Kylie J. Walters,
Patrycja Lech,
Amanda Goh,
Qinghua Wang,
Peter M. Howley
Publication year - 2003
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1634989100
Subject(s) - protein subunit , ubiquitin , proteasome , protein structure , plasma protein binding , linker , dna , nucleotide , biology , dna binding protein , binding site , biochemistry , nucleotide excision repair , dna repair , microbiology and biotechnology , biophysics , chemistry , transcription factor , gene , computer science , operating system
The Rad23 family of proteins, including the human homologs hHR23a and hHR23b, stimulates nucleotide excision repair and has been shown to provide a novel link between proteasome-mediated protein degradation and DNA repair. In this work, we illustrate how the proteasomal subunit S5a regulates hHR23a protein structure. By using NMR spectroscopy, we have elucidated the structure and dynamic properties of the 40-kDa hHR23a protein and show it to contain four structured domains connected by flexible linker regions. In addition, we reveal that these domains interact in an intramolecular fashion, and by using residual dipolar coupling data in combination with chemical shift perturbation analysis, we present the hHR23a structure. By itself, hHR23a adopts a closed conformation defined by the interaction of an N-terminal ubiquitin-like domain with two ubiquitin-associated domains. Interestingly, binding of the proteasomal subunit S5a disrupts the hHR23a interdomain interactions and thereby causes it to adopt an opened conformation.