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-Structure paper
| タイトル | Nucleotide-dependent conformational changes direct peptide export by the transporter associated with antigen processing. |
|---|---|
| ジャーナル・号・ページ | Immunity, Vol. 58, Issue 9, Page 2166-22175.e4, Year 2025 |
| 掲載日 | 2025年9月9日 |
著者 | James Lee / Victor Manon / Jue Chen / ![]() |
| PubMed 要旨 | 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 ...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. |
リンク | Immunity / PubMed:40885191 / PubMed Central |
| 手法 | EM (単粒子) |
| 解像度 | 3.1 - 3.7 Å |
| 構造データ | EMDB-49045, PDB-9n61: EMDB-49046, PDB-9n62: EMDB-49047, PDB-9n63: EMDB-49048, PDB-9n64: EMDB-49049, PDB-9n65: EMDB-49050, PDB-9n66: |
| 化合物 | ![]() ChemComp-ATP: ![]() ChemComp-MG: ![]() ChemComp-HOH: ![]() ChemComp-ADP: |
| 由来 |
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キーワード | MEMBRANE PROTEIN / ABC transporter / antigen processing / peptide transporter |
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