7D99

human potassium-chloride co-transporter KCC4

7D99 の概要

• エントリーDOI: 10.2210/pdb7d99/pdb
• EMDBエントリー: 30617
• 分子名称: potassium-chloride co-transporter KCC4, 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, co-transporter, transport protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 248056.60

構造登録者

Xie, Y.,Chang, S.,Zhao, C.,Ye, S.,Guo, J. (登録日: 2020-10-12, 公開日: 2020-12-30, 最終更新日: 2024-10-30)

主引用文献

Xie, Y.,Chang, S.,Zhao, C.,Wang, F.,Liu, S.,Wang, J.,Delpire, E.,Ye, S.,Guo, J.
Structures and an activation mechanism of human potassium-chloride cotransporters.
Sci Adv, 6:-, 2020

PubMed Abstract: Potassium-chloride cotransporters KCC1 to KCC4 mediate the coupled export of potassium and chloride across the plasma membrane and play important roles in cell volume regulation, auditory system function, and γ-aminobutyric acid (GABA) and glycine-mediated inhibitory neurotransmission. Here, we present 2.9- to 3.6-Å resolution structures of full-length human KCC2, KCC3, and KCC4. All three KCCs adopt a similar overall architecture, a domain-swap dimeric assembly, and an inward-facing conformation. The structural and functional studies reveal that one unexpected N-terminal peptide binds at the cytosolic facing cavity and locks KCC2 and KCC4 at an autoinhibition state. The C-terminal domain (CTD) directly interacts with the N-terminal inhibitory peptide, and the relative motions between the CTD and the transmembrane domain (TMD) suggest that CTD regulates KCCs' activities by adjusting the autoinhibitory effect. These structures provide the first glimpse of full-length structures of KCCs and an autoinhibition mechanism among the amino acid-polyamine-organocation transporter superfamily.

PubMed: 33310850
DOI: 10.1126/sciadv.abc5883

実験手法

ELECTRON MICROSCOPY (2.9 Å)