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-Structure paper
タイトル | Structure of the Wilson disease copper transporter ATP7B. |
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ジャーナル・号・ページ | Sci Adv, Vol. 8, Issue 9, Page eabl5508, Year 2022 |
掲載日 | 2022年3月4日 |
著者 | Ryan M Bitter / SeCheol Oh / Zengqin Deng / Suhaila Rahman / Richard K Hite / Peng Yuan / |
PubMed 要旨 | ATP7A and ATP7B, two homologous copper-transporting P1B-type ATPases, play crucial roles in cellular copper homeostasis, and mutations cause Menkes and Wilson diseases, respectively. ATP7A/B contains ...ATP7A and ATP7B, two homologous copper-transporting P1B-type ATPases, play crucial roles in cellular copper homeostasis, and mutations cause Menkes and Wilson diseases, respectively. ATP7A/B contains a P-type ATPase core consisting of a membrane transport domain and three cytoplasmic domains, the A, P, and N domains, and a unique amino terminus comprising six consecutive metal-binding domains. Here, we present a cryo-electron microscopy structure of frog ATP7B in a copper-free state. Interacting with both the A and P domains, the metal-binding domains are poised to exert copper-dependent regulation of ATP hydrolysis coupled to transmembrane copper transport. A ring of negatively charged residues lines the cytoplasmic copper entrance that is presumably gated by a conserved basic residue sitting at the center. Within the membrane, a network of copper-coordinating ligands delineates a stepwise copper transport pathway. This work provides the first glimpse into the structure and function of ATP7 proteins and facilitates understanding of disease mechanisms and development of rational therapies. |
リンク | Sci Adv / PubMed:35245129 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.19 - 3.49 Å |
構造データ | EMDB-25137, PDB-7si3: EMDB-25138, PDB-7si6: EMDB-25139, PDB-7si7: |
化合物 | ChemComp-MG: ChemComp-ALF: |
由来 |
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キーワード | METAL TRANSPORT/Translocase / Copper transport / Wilson disease / METAL TRANSPORT / METAL TRANSPORT-Translocase complex / Translocase |