- PDB-7pqg: Structure of thermostabilised human NTCP in complex with nanobody 87 -
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基本情報
登録情報
データベース: PDB / ID: 7pqg
タイトル
Structure of thermostabilised human NTCP in complex with nanobody 87
要素
Nanobody 87
Sodium/bile acid cotransporter
キーワード
MEMBRANE PROTEIN / SLC10A1 / sodium bile acid symporter
機能・相同性
機能・相同性情報
bile acid:sodium symporter activity / regulation of bile acid secretion / bile acid and bile salt transport / bile acid signaling pathway / Recycling of bile acids and salts / response to nutrient levels / response to organic cyclic compound / response to estrogen / cellular response to xenobiotic stimulus / virus receptor activity ...bile acid:sodium symporter activity / regulation of bile acid secretion / bile acid and bile salt transport / bile acid signaling pathway / Recycling of bile acids and salts / response to nutrient levels / response to organic cyclic compound / response to estrogen / cellular response to xenobiotic stimulus / virus receptor activity / basolateral plasma membrane / response to ethanol / plasma membrane 類似検索 - 分子機能
Bile acid:sodium symporter/arsenical resistance protein Acr3 / Bile acid:sodium symporter / Sodium Bile acid symporter family / Sodium/solute symporter superfamily 類似検索 - ドメイン・相同性
ジャーナル: Nature / 年: 2022 タイトル: Structural basis of sodium-dependent bile salt uptake into the liver. 著者: Kapil Goutam / Francesco S Ielasi / Els Pardon / Jan Steyaert / Nicolas Reyes / 要旨: The liver takes up bile salts from blood to generate bile, enabling absorption of lipophilic nutrients and excretion of metabolites and drugs. Human Na-taurocholate co-transporting polypeptide (NTCP) ...The liver takes up bile salts from blood to generate bile, enabling absorption of lipophilic nutrients and excretion of metabolites and drugs. Human Na-taurocholate co-transporting polypeptide (NTCP) is the main bile salt uptake system in liver. NTCP is also the cellular entry receptor of human hepatitis B and D viruses (HBV/HDV), and has emerged as an important target for antiviral drugs. However, the molecular mechanisms underlying NTCP transport and viral receptor functions remain incompletely understood. Here we present cryo-electron microscopy structures of human NTCP in complexes with nanobodies, revealing key conformations of its transport cycle. NTCP undergoes a conformational transition opening a wide transmembrane pore that serves as the transport pathway for bile salts, and exposes key determinant residues for HBV/HDV binding to the outside of the cell. A nanobody that stabilizes pore closure and inward-facing states impairs recognition of the HBV/HDV receptor-binding domain preS1, demonstrating binding selectivity of the viruses for open-to-outside over inward-facing conformations of the NTCP transport cycle. These results provide molecular insights into NTCP 'gated-pore' transport and HBV/HDV receptor recognition mechanisms, and are expected to help with development of liver disease therapies targeting NTCP.