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-Structure paper
タイトル | Molecular Structure of the Human CFTR Ion Channel. |
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ジャーナル・号・ページ | Cell, Vol. 169, Issue 1, Page 85-95.e8, Year 2017 |
掲載日 | 2017年3月23日 |
著者 | Fangyu Liu / Zhe Zhang / László Csanády / David C Gadsby / Jue Chen / |
PubMed 要旨 | The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-binding cassette (ABC) transporter that uniquely functions as an ion channel. Here, we present a 3.9 Å structure of ...The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP-binding cassette (ABC) transporter that uniquely functions as an ion channel. Here, we present a 3.9 Å structure of dephosphorylated human CFTR without nucleotides, determined by electron cryomicroscopy (cryo-EM). Close resemblance of this human CFTR structure to zebrafish CFTR under identical conditions reinforces its relevance for understanding CFTR function. The human CFTR structure reveals a previously unresolved helix belonging to the R domain docked inside the intracellular vestibule, precluding channel opening. By analyzing the sigmoid time course of CFTR current activation, we propose that PKA phosphorylation of the R domain is enabled by its infrequent spontaneous disengagement, which also explains residual ATPase and gating activity of dephosphorylated CFTR. From comparison with MRP1, a feature distinguishing CFTR from all other ABC transporters is the helix-loop transition in transmembrane helix 8, which likely forms the structural basis for CFTR's channel function. |
リンク | Cell / PubMed:28340353 |
手法 | EM (単粒子) |
解像度 | 3.87 Å |
構造データ | PDB-5uak: |
由来 |
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キーワード | MEMBRANE PROTEIN (膜タンパク質) / HYDROLASE (加水分解酵素) / ABC transporter / anion channel (イオンチャネル) / cystic fibrosis (嚢胞性線維症) |