9N62

Transporter associated with antigen processing (TAP) EQ mutant bound to ATP in the inward-facing state

Summary for 9N62

• Entry DOI: 10.2210/pdb9n62/pdb
• EMDB information: 49046
• Descriptor: Antigen peptide transporter 1, Antigen peptide transporter 2, ADENOSINE-5'-TRIPHOSPHATE (3 entities in total)
• Functional Keywords: abc transporter, antigen processing, peptide transporter, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 157785.16

Authors

Lee, J.,Chen, J. (deposition date: 2025-02-04, release date: 2025-09-03, Last modification date: 2026-03-18)

Primary citation

Lee, J.,Manon, V.,Chen, J.
Nucleotide-dependent conformational changes direct peptide export by the transporter associated with antigen processing.
Immunity, 58:2166-2175.e4, 2025

PubMed Abstract: The transporter associated with antigen processing (TAP) delivers peptide antigens from the cytoplasm into the endoplasmic reticulum (ER) for loading onto major histocompatibility complex class I (MHC-I) molecules. To examine the mechanisms of peptide transport and release into the ER, we determined cryo-electron microscopy structures of the human TAP heterodimer in multiple functional states along the transport cycle. In the inward-facing conformation, when the peptide translocation cavity within the TAP heterodimer is exposed to the cytosol, ATP binding strengthened intradomain assembly. Transition to the outward-facing conformation, when the transporter opens to the ER lumen, led to a complete reconfiguration of the peptide-binding site, facilitating peptide release. ATP hydrolysis opened the catalytically active nucleotide-binding consensus site, and the subsequent separation of the nucleotide-binding domains reset the transport cycle. These findings establish a comprehensive structural framework for understanding unilateral peptide transport, vanadate trapping, and trans-inhibition-an internal feedback mechanism that prevents excessive peptide accumulation and activation of the ER stress response.

PubMed: 40885191
DOI: 10.1016/j.immuni.2025.08.003

Experimental method

ELECTRON MICROSCOPY (3.4 Å)