PDBsum entry 1qze

Replication

PDB id: 1qze

Contents

Protein chain

214 a.a. *

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Dna-Repair protein hhr23a alters its protein structure upon binding proteasomal subunit s5a.

Authors

K.J.Walters, P.J.Lech, A.M.Goh, Q.Wang, P.M.Howley.

Ref.

Proc Natl Acad Sci U S A, 2003, 100, 12694-12699. [DOI no: 10.1073/pnas.1634989100]

PubMed id

14557549

Abstract

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.

Figure 3.
Fig. 3. The S5a contact surface on the UBL domain overlaps significantly with that used to bind the UBA domains. (A) Residues whose amide protons showed NOE interaction with S5a (196-307) are colored blue. (B) Those that shift upon addition of either UBA domain are colored dark blue, and those that only shift upon addition of the UBA2 domain are light blue. (Left) The orientation is identical to that of Fig. 1B (Left), and these are rotated 180° (Right). The program GRASP (51) was used.

Figure 4.
Fig. 4. Model of S5a-induced conformational change in hHR23a. In the absence of S5a, hHR23a undergoes conformational exchange between two states as each of the UBA domains competes for the same binding surface on the UBL domain. Addition of S5a causes hHR23a to adopt an opened conformation as S5a blocks the UBA-binding surface of the UBL domain.