Structural basis of sodium-dependent bile salt uptake into the liver
| dc.rights.license | open | en_US |
| hal.structure.identifier | Microbiologie Fondamentale et Pathogénicité [MFP] | |
| dc.contributor.author | GOUTAM, Kapil | |
| hal.structure.identifier | Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) [IAB] | |
| dc.contributor.author | IELASI, Francesco | |
| hal.structure.identifier | Structural Biology Brussels [SBB] | |
| dc.contributor.author | PARDON, Els | |
| hal.structure.identifier | Structural Biology Brussels [SBB] | |
| dc.contributor.author | STEYAERT, Jan | |
| hal.structure.identifier | Institut Européen de Chimie et de Biologie | |
| hal.structure.identifier | Microbiologie Fondamentale et Pathogénicité [MFP] | |
| dc.contributor.author | REYES, Nicolas | |
| dc.date.accessioned | 2024-09-05T06:42:10Z | |
| dc.date.available | 2024-09-05T06:42:10Z | |
| dc.date.issued | 2022 | |
| dc.identifier.issn | 0028-0836 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/201444 | |
| dc.description.abstractEn | 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 2,3 (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. | |
| dc.language.iso | EN | en_US |
| dc.title.en | Structural basis of sodium-dependent bile salt uptake into the liver | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1038/s41586-022-04723-z | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Hépatologie et Gastroentérologie | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Biologie structurale [q-bio.BM] | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Médecine humaine et pathologie/Maladies infectieuses | en_US |
| dc.identifier.pubmed | 35545671 | en_US |
| bordeaux.journal | Nature | en_US |
| bordeaux.page | 1015-1020 | en_US |
| bordeaux.volume | 606 | en_US |
| bordeaux.hal.laboratories | MFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234 | en_US |
| bordeaux.issue | 7916 | en_US |
| bordeaux.institution | CNRS | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| bordeaux.import.source | hal | |
| hal.identifier | hal-04688088 | |
| hal.version | 1 | |
| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | false | |
| workflow.import.source | hal | |
| dc.rights.cc | Pas de Licence CC | en_US |
| bordeaux.COinS | ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nature&rft.date=2022&rft.volume=606&rft.issue=7916&rft.spage=1015-1020&rft.epage=1015-1020&rft.eissn=0028-0836&rft.issn=0028-0836&rft.au=GOUTAM,%20Kapil&IELASI,%20Francesco&PARDON,%20Els&STEYAERT,%20Jan&REYES,%20Nicolas&rft.genre=article |
