PDBsum entry 1uel

Gene regulation/protein binding

PDB id: 1uel

Contents

Protein chains

95 a.a. *

48 a.a. *

* Residue conservation analysis

PDB id:

1uel

Name:

Gene regulation/protein binding

Title:

Solution structure of ubiquitin-like domain of hhr23b complexed with ubiquitin-interacting motif of proteasome subunit s5a

Structure:

Uv excision repair protein rad23 homolog b. Chain: a. Fragment: ubiquitin-like domain (residues 1-95). Synonym: hhr23b. Engineered: yes. 26s proteasome non-atpase regulatory subunit 4. Chain: b. Fragment: ubiquitin-interacting motif (residues 201-248). Synonym: s5a, 26s proteasome regulatory subunit s5a.

Source:

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

NMR struc:

20 models

Authors:

K.Fujiwara,T.Tenno,J.G.Jee,K.Sugasawa,I.Ohki,C.Kojima,H.Tochio, H.Hiroaki,H.Hanaoka,M.Shirakawa,Riken Structural Genomics/proteomics Initiative (Rsgi)

Key ref:

K.Fujiwara et al. (2004). Structure of the ubiquitin-interacting motif of S5a bound to the ubiquitin-like domain of HR23B. J Biol Chem, 279, 4760-4767. PubMed id: 14585839 DOI: 10.1074/jbc.M309448200

Date:

19-May-03 Release date: 10-Feb-04

Protein chain

P54727  (RD23B_HUMAN) -  UV excision repair protein RAD23 homolog B from Homo sapiens

Seq: 409 a.a.

Struc: 95 a.a.*

Protein chain

P55036  (PSMD4_HUMAN) -  26S proteasome non-ATPase regulatory subunit 4 from Homo sapiens

Seq: 377 a.a.

Struc: 48 a.a.*

* PDB and UniProt seqs differ at 11 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

DOI no: 10.1074/jbc.M309448200

J Biol Chem 279:4760-4767 (2004)

PubMed id: 14585839

Structure of the ubiquitin-interacting motif of S5a bound to the ubiquitin-like domain of HR23B.

K.Fujiwara, T.Tenno, K.Sugasawa, J.G.Jee, I.Ohki, C.Kojima, H.Tochio, H.Hiroaki, F.Hanaoka, M.Shirakawa.

ABSTRACT

Ubiquitination, a modification in which single or multiple ubiquitin molecules are attached to a protein, serves signaling functions that control several cellular processes. The ubiquitination signal is recognized by downstream effectors, many of which carry a ubiquitin-interacting motif (UIM). Such interactions can be modulated by regulators carrying a ubiquitin-like (UbL) domain, which binds UIM by mimicking ubiquitination. Of them, HR23B regulates the proteasomal targeting of ubiquitinated substrates, DNA repair factors, and other proteins. Here we report the structure of the UIM of the proteasome subunit S5a bound to the UbL domain of HR23B. The UbL domain presents one hydrophobic and two polar contact sites for interaction with UIM. The residues in these contact sites are well conserved in ubiquitin, but ubiquitin also presents a histidine at the interface. The pH-dependent protonation of this residue interferes with the access of ubiquitin to the UIM and the ubiquitin-associated domain (UBA), and its mutation to a smaller residue increases the affinity of ubiquitin for UIM.

Selected figure(s)

Figure 1.
FIG. 1. Sequence alignment of UbL and UIM. a, sequences of human HR23B UbL and human ubiquitin. b, sequence alignment of the C-terminal UIM of human proteasome subunit S5a with UIMs of endocytic factors that have been either shown or implied to bind a ubiquitin tag (top panel) and of the N-terminal UIMs of human and S. cerevisiae S5a (Rpn10p) (bottom panel). The sequences are from human (hs), mouse (mm), Drosophila melanogaster (dm), and S. cerevisiae (sc). In a and b, identical residues are highlighted in black, and homologous residues are highlighted in gray. Secondary structural elements of HR23B UbL and S5a UIM are indicated. The residues shown to be important for the complex formation through structural or mutational analyses are marked with asterisks.

Figure 3.
FIG. 3. Structure of the UIM-UbL complex. a, ribbon diagram of the lowest energy structure. UIM and UbL are colored orange and blue, respectively. Secondary structural elements of UbL are indicated. The Tyr48-Ala^49-Gly50 segment of UbL, which forms [T] conformation, is shown in green. b, surface representation of the binding sites of UbL bound to UIM. Hydrophobic and charged residues are shown in yellow and red, respectively, and the [T] segment is shown in green. The side chains of UIM residues that interact with UbL are also shown. c, schematic diagram of the contacts between UIM and UbL. The main chain of UIM is shown in red. The side chains of UIM and UbL residues that form the interface are shown in black and green, respectively. Hydrophobic contacts are indicated by blue dotted lines, and hydrogen bonds and charged interactions are indicated by red dashed lines. Me denotes a methyl group. d, conserved UIM-binding sites in ubiquitin, deduced from the structure of the UIM-UbL complex, are shown on a model of the complex between human ubiquitin and UIM. Hydrophobic and charged residues are colored yellow and red, respectively, on the surface representation of human ubiquitin. The [T] segment, Phe^45-Ala^46-Gly47, is shown in green. His68, which causes the protrusion, is shown in blue. The model was constructed by best fit superposition of the coordinates of human ubiquitin (Protein Data Bank code 1d3z [PDB] ) to those of UbL in the lowest energy structure of the UIM-UbL complex.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2004, 279, 4760-4767) copyright 2004.

Figures were selected by an automated process.