4PWN

Crystal structure of Active WNK1 kinase

4PWN の概要

• エントリーDOI: 10.2210/pdb4pwn/pdb
• 関連するPDBエントリー: 3FPQ 4Q2A
• 分子名称: Serine/threonine-protein kinase WNK1, PHOSPHATE ION (3 entities in total)
• 機能のキーワード: kinase, wnk1, ser/thr protein kinase, serine/threonine kinase, atp-binding, phosphorylation, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : Q9H4A3
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 31633.52

構造登録者

Piala, A.,Moon, T.,Akella, T.,He, H.,Cobbm, M.H.,Goldsmith, E. (登録日: 2014-03-20, 公開日: 2014-05-28, 最終更新日: 2023-09-20)

主引用文献

Piala, A.T.,Moon, T.M.,Akella, R.,He, H.,Cobb, M.H.,Goldsmith, E.J.
Chloride Sensing by WNK1 Involves Inhibition of Autophosphorylation.
Sci.Signal., 7:ra41-ra41, 2014

PubMed Abstract: WNK1 [with no lysine (K)] is a serine-threonine kinase associated with a form of familial hypertension. WNK1 is at the top of a kinase cascade, leading to phosphorylation of several cotransporters, in particular those transporting sodium, potassium, and chloride (NKCC), sodium and chloride (NCC), and potassium and chloride (KCC). The responsiveness of NKCC, NCC, and KCC to changes in extracellular chloride parallels their phosphorylation state, provoking the proposal that these transporters are controlled by a chloride-sensitive protein kinase. We found that chloride stabilizes the inactive conformation of WNK1, preventing kinase autophosphorylation and activation. Crystallographic studies of inactive WNK1 in the presence of chloride revealed that chloride binds directly to the catalytic site, providing a basis for the unique position of the catalytic lysine. Mutagenesis of the chloride-binding site rendered the kinase less sensitive to inhibition of autophosphorylation by chloride, validating the binding site. Thus, these data suggest that WNK1 functions as a chloride sensor through direct binding of a regulatory chloride ion to the active site, which inhibits autophosphorylation.

PubMed: 24803536
DOI: 10.1126/scisignal.2005050

実験手法

X-RAY DIFFRACTION (1.84 Å)