- PDB-7d99: human potassium-chloride co-transporter KCC4 -
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基本情報
登録情報
データベース: PDB / ID: 7d99
タイトル
human potassium-chloride co-transporter KCC4
要素
potassium-chloride co-transporter KCC4
キーワード
TRANSPORT PROTEIN / potassium-chloride / co-transporter
機能・相同性
機能・相同性情報
potassium:chloride symporter activity / Cation-coupled Chloride cotransporters / chloride ion homeostasis / potassium ion homeostasis / cell volume homeostasis / potassium ion import across plasma membrane / monoatomic ion transport / potassium ion transmembrane transport / chloride transmembrane transport / cellular response to glucose stimulus ...potassium:chloride symporter activity / Cation-coupled Chloride cotransporters / chloride ion homeostasis / potassium ion homeostasis / cell volume homeostasis / potassium ion import across plasma membrane / monoatomic ion transport / potassium ion transmembrane transport / chloride transmembrane transport / cellular response to glucose stimulus / chemical synaptic transmission / synapse / protein kinase binding / protein-containing complex / plasma membrane 類似検索 - 分子機能
National Natural Science Foundation of China (NSFC)
31870724
中国
引用
ジャーナル: Sci Adv / 年: 2020 タイトル: Structures and an activation mechanism of human potassium-chloride cotransporters. 著者: Yuan Xie / Shenghai Chang / Cheng Zhao / Feng Wang / Si Liu / Jin Wang / Eric Delpire / Sheng Ye / Jiangtao Guo / 要旨: 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 ...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.