1IM3

Crystal Structure of the human cytomegalovirus protein US2 bound to the MHC class I molecule HLA-A2/tax

Summary for 1IM3

• Entry DOI: 10.2210/pdb1im3/pdb
• Descriptor: HLA CLASS I HISTOCOMPATIBILITY ANTIGEN, A-2 ALPHA CHAIN, beta-2-microglobulin, Human T-cell lymphotropic virus type 1 Tax peptide, ... (5 entities in total)
• Functional Keywords: beta sheet, beta sandwhich, immunoglobulin (ig) fold, immunoglobulin (ig)-like domain, protein complex, alpha helix, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P01892; Secreted: P61769; Host endoplasmic reticulum membrane; Single- pass type I membrane protein: P09713
• Total number of polymer chains: 16
• Total formula weight: 222813.10

Authors

Gewurz, B.E.,Gaudet, R.,Tortorella, D.,Wang, E.W.,Ploegh, H.L.,Wiley, D.C. (deposition date: 2001-05-09, release date: 2001-06-06, Last modification date: 2024-11-20)

Primary citation

Gewurz, B.E.,Gaudet, R.,Tortorella, D.,Wang, E.W.,Ploegh, H.L.,Wiley, D.C.
Antigen presentation subverted: Structure of the human cytomegalovirus protein US2 bound to the class I molecule HLA-A2.
Proc.Natl.Acad.Sci.USA, 98:6794-6799, 2001

PubMed Abstract: Many persistent viruses have evolved the ability to subvert MHC class I antigen presentation. Indeed, human cytomegalovirus (HCMV) encodes at least four proteins that down-regulate cell-surface expression of class I. The HCMV unique short (US)2 glycoprotein binds newly synthesized class I molecules within the endoplasmic reticulum (ER) and subsequently targets them for proteasomal degradation. We report the crystal structure of US2 bound to the HLA-A2/Tax peptide complex. US2 associates with HLA-A2 at the junction of the peptide-binding region and the alpha3 domain, a novel binding surface on class I that allows US2 to bind independently of peptide sequence. Mutation of class I heavy chains confirms the importance of this binding site in vivo. Available data on class I-ER chaperone interactions indicate that chaperones would not impede US2 binding. Unexpectedly, the US2 ER-luminal domain forms an Ig-like fold. A US2 structure-based sequence alignment reveals that seven HCMV proteins, at least three of which function in immune evasion, share the same fold as US2. The structure allows design of further experiments to determine how US2 targets class I molecules for degradation.

PubMed: 11391001
DOI: 10.1073/pnas.121172898

Experimental method

X-RAY DIFFRACTION (2.2 Å)