PDBsum entry: 1oqy

Replication

PDB-id: 1oqy

Contents

Description

Header details

Header records

References

PROCHECK

Protein chain

363 a.a. *

* Residue conservation analysis

Tools

Clefts Calculation

PDB id:

1oqy

Name:

Replication

Title:

Structure of the DNA repair protein hhr23a

Structure:

Uv excision repair protein rad23 homolog a. Chain: a. Synonym: hhr23a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: rad23a. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

UniProt:

P54725 (RD23A_HUMAN)

Seq:

Struc:

Seq:

363 a.a.

Struc:

363 a.a.*

Key:	PfamA domain
Secondary structure	CATH domain

* PDB and UniProt seqs differ at 1 residue position (black cross)

Resolution:

not givenÅ

NMR structure:

12 models

Authors:

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

Key ref:

K.J.Walters et al. (2003). DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a.. Proc Natl Acad Sci U S A, 100, 12694-12699. [PubMed id: 14557549] [DOI: 10.1073/pnas.1634989100]

Date:

11-Mar-03

Release date:

21-Oct-03

Related entries:

1qze
hhr23a protein structure based on residual dipolar coupling
data

Quick_links

Procheck

Clefts

Surface

Key reference

DOI no: 10.1073/pnas.1634989100

Proc Natl Acad Sci U S A 100:12694-12699 (2003)

PubMed id: 14557549

DNA-repair protein hHR23a alters its protein structure upon binding proteasomal subunit S5a.

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

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.

Selected figure(s)

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.

Figures were selected by an automated process.