9DW5

Dephosphorylated CFTR in 1:1 complex with PKA-C (site I)

9DW5 の概要

• エントリーDOI: 10.2210/pdb9dw5/pdb
• EMDBエントリー: 47236
• 分子名称: Cystic fibrosis transmembrane conductance regulator, cAMP-dependent protein kinase catalytic subunit alpha, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: cftr, pka, complex, hydrolase
• 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: 209647.89

構造登録者

Fiedorczuk, K.,Chen, J.,Csanady, L. (登録日: 2024-10-08, 公開日: 2024-11-13, 最終更新日: 2025-05-14)

主引用文献

Fiedorczuk, K.,Iordanov, I.,Mihalyi, C.,Szollosi, A.,Csanady, L.,Chen, J.
The structures of protein kinase A in complex with CFTR: Mechanisms of phosphorylation and noncatalytic activation.
Proc.Natl.Acad.Sci.USA, 121:e2409049121-e2409049121, 2024

PubMed Abstract: Protein kinase A (PKA) is a key regulator of cellular functions by selectively phosphorylating numerous substrates, including ion channels, enzymes, and transcription factors. It has long served as a model system for understanding the eukaryotic kinases. Using cryoelectron microscopy, we present complex structures of the PKA catalytic subunit (PKA-C) bound to a full-length protein substrate, the cystic fibrosis transmembrane conductance regulator (CFTR)-an ion channel vital to human health. CFTR gating requires phosphorylation of its regulatory (R) domain. Unphosphorylated CFTR engages PKA-C at two locations, establishing two "catalytic stations" near to, but not directly involving, the R domain. This configuration, coupled with the conformational flexibility of the R domain, permits transient interactions of the eleven spatially separated phosphorylation sites. Furthermore, we determined two structures of the open-pore CFTR stabilized by PKA-C, providing a molecular basis to understand how PKA-C stimulates CFTR currents even in the absence of phosphorylation.

PubMed: 39495916
DOI: 10.1073/pnas.2409049121

実験手法

ELECTRON MICROSCOPY (3.8 Å)