Volume 32, No 8, Aug 2022

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 32 Issue 8, August 2022: 773-776   |  Open Access

LETTERS TO THE EDITOR

Structure of human NTCP reveals the basis of recognition and sodium-driven transport of bile salts into the liver

Hongtao Liu¹ , Rossitza N. Irobalieva¹ , Rose Bang-Sørensen¹ , Kamil Nosol¹ , Somnath Mukherjee² , Parth Agrawal² , Bruno Stieger³ , Anthony A. Kossiakoff² , Kaspar P. Locher^1,*

¹Institute of Molecular Biology and Biophysics, ETH Zürich, Zürich, Switzerland
²Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL, USA
³Department of Clinical Pharmacology and Toxicology, University Hospital Zürich, University of Zürich, Zürich, Switzerland
Correspondence: Kaspar P. Locher(locher@mol.biol.ethz.ch)

Dear Editor,

The sodium taurocholate (TC) co-transporting polypeptide NTCP (SLC10A1) is a secondary active membrane transport protein that mediates the uptake of bile salts from the portal blood plasma into the cytoplasm of liver cells. NTCP was originally cloned from rat and demonstrated to be localized in the basolateral membrane.1 Its activity is a key component of bile acid homeostasis and enterohepatic circulation of bile salts (Fig. 1a), a process that includes at least three additional transporter proteins, namely BSEP, ASBT and OSTα/β.2,3 In addition to its role in mediating bile salt uptake, NTCP also serves as the receptor of the human hepatitis B and D viruses.4 The mechanism by which NTCP recognizes and transports bile salts is not understood, in part because no structural insight into the interaction of NTCP with its substrates is available. While recent studies reported structures of NTCP bound to inhibitory nanobodies5 or Fab fragments,6,7 no substrate-binding pockets were identified.

https://doi.org/10.1038/s41422-022-00680-4

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