9N65

Transporter associated with antigen processing (TAP) bound to ATP and ADP In the inward-facing conformation

9N65 の概要

• エントリーDOI: 10.2210/pdb9n65/pdb
• EMDBエントリー: 49049
• 分子名称: Antigen peptide transporter 1, Antigen peptide transporter 2, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: abc transporter, antigen processing, peptide transporter, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 157753.79

構造登録者

Lee, J.,Manon, V.,Chen, J. (登録日: 2025-02-04, 公開日: 2025-09-03, 最終更新日: 2026-03-18)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.7 Å)