PDBsum entry 3d2u

Immune system

PDB id: 3d2u

Contents

Protein chains

281 a.a. *

99 a.a. *

182 a.a. *

Ligands

ALA-LEU-PRO-HIS-ALA-ILE-LEU-ARG-LEU ×2

NAG-NAG ×3

MAN

BMA

FUC

NAG ×7

Waters ×362

* Residue conservation analysis

PDB id:

3d2u

Name:

Immune system

Title:

Structure of ul18, a peptide-binding viral mhc mimic, bound to a host inhibitory receptor

Structure:

Ul18 protein. Chain: a, e. Fragment: sequence database residues 21-301. Beta-2-microglobulin. Chain: b, f. Leukocyte immunoglobulin-like receptor subfamily b member 1. Chain: d, h. Fragment: ig-like c2-type 1 and c2-type 2 domains.

Source:

Human herpesvirus 5. Human cytomegalovirus. Organism_taxid: 10359. Strain: ad169. Other_details: gene ul18. Homo sapiens. Human. Organism_taxid: 9606. Other_details: beta2m.

Resolution:

2.21Å R-factor: 0.241 R-free: 0.259

Authors:

Z.Yang,P.J.Bjorkman

Key ref:

Z.Yang and P.J.Bjorkman (2008). Structure of UL18, a peptide-binding viral MHC mimic, bound to a host inhibitory receptor. Proc Natl Acad Sci U S A, 105, 10095-10100. PubMed id: 18632577 DOI: 10.1073/pnas.0804551105

Date:

08-May-08 Release date: 08-Jul-08

Protein chains

P08560  (UL18_HCMVA) -  Glycoprotein UL18 from Human cytomegalovirus (strain AD169)

Seq: 368 a.a.

Struc: 281 a.a.*

Protein chains

P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens

Seq: 119 a.a.

Struc: 99 a.a.

Protein chains

Q8NHL6  (LIRB1_HUMAN) -  Leukocyte immunoglobulin-like receptor subfamily B member 1 from Homo sapiens

Seq: 650 a.a.

Struc: 182 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

DOI no: 10.1073/pnas.0804551105

Proc Natl Acad Sci U S A 105:10095-10100 (2008)

PubMed id: 18632577

Structure of UL18, a peptide-binding viral MHC mimic, bound to a host inhibitory receptor.

Z.Yang, P.J.Bjorkman.

ABSTRACT

UL18 is a human cytomegalovirus class I MHC (MHCI) homolog that binds the host inhibitory receptor LIR-1 and the only known viral MHC homolog that presents peptides. The 2.2-A structure of a LIR-1/UL18/peptide complex reveals increased contacts and optimal surface complementarity in the LIR-1/UL18 interface compared with LIR/MHCI interfaces, resulting in a >1,000-fold higher affinity. Despite sharing only approximately 25% sequence identity, UL18's structure and peptide binding are surprisingly similar to host MHCI. The crystal structure suggests that most of the UL18 surface, except where LIR-1 and the host-derived light chain bind, is covered by carbohydrates attached to 13 potential N-glycosylation sites, thereby preventing access to bound peptide and association with most MHCI-binding proteins. The LIR-1/UL18 structure demonstrates how a viral protein evolves from its host ancestor to impede unwanted interactions while preserving and improving its receptor-binding site.

Selected figure(s)

Figure 4.
Surface representations of LIR proteins and their binding partners. Contact surfaces (≤4.0 Å) are highlighted in yellow. (A) UL18, UL18/LIR-1, and LIR-1. An asterisk marks the position of a LIR-1 loop (residues 148–154) that is disordered in the UL18/LIR-1 complex structure. (B) HLA-A2, HLA-A2/LIR-1, and LIR-1 (PDB ID code 1P7Q). (C) HLA-G, HLA-G/LIR-2, and LIR-2 (PDB ID code 2DYP).

Figure 5.
Interaction sites for potential binding partners highlighted on a fully glycosylated UL18 model. (A) Space-filling representation of the UL18/LIR-1 complex (UL18 in magenta, β2m in slate, peptide in light green, LIR-1 in cyan) with a complex carbohydrate model (yellow) attached to each of the 13 potential N-glycosylation sites. The single predicted O-glycosylation site (residue 281) within the UL18 ectodomain is indicated by an orange sphere. Two to three additional O-glycosylation sites are predicted in the region C-terminal to the UL18 ectodomain fragment that was crystallized, but these sites would be distant from the binding sites for all potential UL18 binding partners. The UL18 counterparts of the approximate binding sites on a class I MHC molecule for a TCR or KIR are indicated by arrows. (B) Top view of the fully glycosylated UL18 peptide binding platform. (C) Potential US2 binding site (dark green) on fully glycosylated UL18. (D) Potential CD8 binding site (dark green) on fully glycosylated UL18. An enlarged view of the CD8-binding loop in the class I MHC α3 domain (gray) is shown with the counterpart UL18 loop (magenta).

Figures were selected by an automated process.