6UKN

Cryo-EM structure of the potassium-chloride cotransporter KCC4 in lipid nanodiscs

6UKN の概要

• エントリーDOI: 10.2210/pdb6ukn/pdb
• EMDBエントリー: 20807
• 分子名称: Solute carrier family 12 member 7, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, POTASSIUM ION, ... (4 entities in total)
• 機能のキーワード: potassium chloride cotransporter, slc12, transport protein
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 121858.60

構造登録者

Reid, M.S.,Kern, D.M.,Brohawn, S.G. (登録日: 2019-10-05, 公開日: 2020-06-10, 最終更新日: 2024-10-23)

主引用文献

Reid, M.S.,Kern, D.M.,Brohawn, S.G.
Cryo-EM structure of the potassium-chloride cotransporter KCC4 in lipid nanodiscs.
Elife, 9:-, 2020

PubMed Abstract: Cation-chloride-cotransporters (CCCs) catalyze transport of Cl with K and/or Naacross cellular membranes. CCCs play roles in cellular volume regulation, neural development and function, audition, regulation of blood pressure, and renal function. CCCs are targets of clinically important drugs including loop diuretics and their disruption has been implicated in pathophysiology including epilepsy, hearing loss, and the genetic disorders Andermann, Gitelman, and Bartter syndromes. Here we present the structure of a CCC, the K-Cl cotransporter (KCC) KCC4, in lipid nanodiscs determined by cryo-EM. The structure, captured in an inside-open conformation, reveals the architecture of KCCs including an extracellular domain poised to regulate transport activity through an outer gate. We identify binding sites for substrate K and Cl ions, demonstrate the importance of key coordinating residues for transporter activity, and provide a structural explanation for varied substrate specificity and ion transport ratio among CCCs. These results provide mechanistic insight into the function and regulation of a physiologically important transporter family.

PubMed: 32286222
DOI: 10.7554/eLife.52505

実験手法

ELECTRON MICROSCOPY (3.65 Å)