PDBsum entry 1ify

DNA binding protein

PDB id: 1ify

Contents

Protein chain

49 a.a. *

* Residue conservation analysis

PDB id:

1ify

Name:

DNA binding protein

Title:

Solution structure of the internal uba domain of hhr23a

Structure:

Uv excision repair protein rad23 homolog a. Chain: a. Fragment: internal uba domain. Synonym: hhr23a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

10 models

Authors:

T.D.Mueller,J.Feigon

Key ref:

T.D.Mueller and J.Feigon (2002). Solution structures of UBA domains reveal a conserved hydrophobic surface for protein-protein interactions. J Mol Biol, 319, 1243-1255. PubMed id: 12079361 DOI: 10.1016/S0022-2836(02)00302-9

Date:

13-Apr-01 Release date: 03-Jul-02

Protein chain

P54725  (RD23A_HUMAN) -  UV excision repair protein RAD23 homolog A from Homo sapiens

Seq: 363 a.a.

Struc: 49 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1016/S0022-2836(02)00302-9

J Mol Biol 319:1243-1255 (2002)

PubMed id: 12079361

Solution structures of UBA domains reveal a conserved hydrophobic surface for protein-protein interactions.

T.D.Mueller, J.Feigon.

ABSTRACT

UBA domains are a commonly occurring sequence motif of approximately 45 amino acid residues that are found in diverse proteins involved in the ubiquitin/proteasome pathway, DNA excision-repair, and cell signaling via protein kinases. The human homologue of yeast Rad23A (HHR23A) is one example of a nucleotide excision-repair protein that contains both an internal and a C-terminal UBA domain. The solution structure of HHR23A UBA(2) showed that the domain forms a compact three-helix bundle. We report the structure of the internal UBA(1) domain of HHR23A. Comparison of the structures of UBA(1) and UBA(2) reveals that both form very similar folds and have a conserved large hydrophobic surface patch. The structural similarity between UBA(1) and UBA(2), in spite of their low level of sequence conservation, leads us to conclude that the structural variability of UBA domains in general is likely to be rather small. On the basis of the structural similarities as well as analysis of sequence conservation, we predict that this hydrophobic surface patch is a common protein-interacting surface present in diverse UBA domains. Furthermore, accumulating evidence that ubiquitin binds to UBA domains leads us to the prediction that the hydrophobic surface patch of UBA domains interacts with the hydrophobic surface on the five-stranded beta-sheet of ubiquitin. Detailed comparison of the structures of the two UBA domains, combined with previous mutagenesis studies, indicates that the binding site of HIV-1 Vpr on UBA(2) does not completely overlap the ubiquitin binding site.

Selected figure(s)

Figure 2.
Figure 2. Stereoviews of the internal UBA domain UBA(1) of HHR23A (SWISS PROT code R23A_HUMAN) (human homologue of RAD23A) showing residues Thr156 to Gly204. (a) Ribbon representation. The three helices are labeled a1, a2, and a3. (b) Superposition of the ten lowest-energy structures. The backbone atoms are shown in black for carbon atoms, blue for nitrogen atoms, and the carbonyl oxygen atoms are omitted. The side-chains for residues forming the hydrophobic core are shown in green. The N-terminal residues 155-160 are disordered and are not shown.

Figure 4.
Figure 4. A potential protein-protein binding interface of UBA domains is built from hydrophobic residues on the surface. (a) Surface representation of UBA(1) (left) using the following color coding: red, acidic amino acid residues Glu and Asp; blue, basic amino acid residues Arg and Lys, orange, polar amino acid residues Asn, Gln, His, Ser and Thr; white, hydrophobic residues Ala, Gly, Phe, Ile, Pro, Met, Leu, Tyr and Val. The major accessible residues on the hydrophobic surface, Met173, Gly174, Y175, L199 and I202, are marked. The size of the epitope is approximately 470 Å2. The right picture shows the orientation of the helical bundle with respect to the surface representation. The hydrophobic surface patch consists mainly of residues from loop 1 between helices 1 and 2 as well as residues from helix 3. (b) For comparison, the surface of UBA(2) is shown in the same orientation as UBA(1), revealing that the location of the hydrophobic epitope is indeed conserved and consists of identical or homologous residues. The C terminus of UBA(2) is not shown, due to its flexibility.

The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 319, 1243-1255) copyright 2002.

Figures were selected by an automated process.