9O94

Transporter associated with antigen processing (TAP) EQ mutant bound to the viral protein bUL49.5 in the outward-facing kinked state

Summary for 9O94

• Entry DOI: 10.2210/pdb9o94/pdb
• EMDB information: 70241
• Descriptor: Antigen peptide transporter 1, Antigen peptide transporter 2, bUL49.5, 15-Ala helix, ... (5 entities in total)
• Functional Keywords: abc transporter, antigen processing, peptide transporter, membrane protein, herpesvirus
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 175492.75

Authors

Lee, J.,Manon, V.,Chen, J. (deposition date: 2025-04-17, release date: 2025-09-10, Last modification date: 2026-03-18)

Primary citation

Lee, J.,Manon, V.,Chen, J.
Structurally diverse viral inhibitors converge on a shared mechanism to stall the antigen transporter TAP.
Proc.Natl.Acad.Sci.USA, 122:e2516676122-e2516676122, 2025

PubMed Abstract: In the host-pathogen arms race, herpesviruses and poxviruses encode proteins that sabotage the transporter associated with antigen processing (TAP), thereby suppressing MHC-I antigen presentation and enabling lifelong infection. Of the five known viral TAP inhibitors, only the herpes simplex virus (HSV) protein ICP47 has been structurally resolved. We now report cryoelectron microscopy structures of TAP in complex with the remaining four: BNLF2a (Epstein-Barr virus), hUS6 (human cytomegalovirus), bUL49.5 (bovine herpesvirus 1), and CPXV012 (cowpox virus), assembling a structural atlas of viral TAP evasion. Despite employing divergent sequences, folds, and conformational targets, these viral inhibitors converge on a common strategy: they stall TAP from the alternating access cycle, precluding peptide entry into the ER and shielding infected cells from cytotoxic T cell surveillance. These findings reveal striking functional convergence and provide a structural framework for rational antiviral design.

PubMed: 40956880
DOI: 10.1073/pnas.2516676122

Experimental method

ELECTRON MICROSCOPY (3.1 Å)