9CY1

Outward-facing OATP1B1 bound to sybody Sb5

Summary for 9CY1

• Entry DOI: 10.2210/pdb9cy1/pdb
• EMDB information: 46004
• Descriptor: Solute carrier organic anion transporter family member 1B1, Sybody 5 (2 entities in total)
• Functional Keywords: solute carrier, sybody, membrane protein, transport protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 95766.49

Authors

Sung, M.W.,Lees, J.A.,Han, S. (deposition date: 2024-08-01, release date: 2025-04-16, Last modification date: 2025-05-28)

Primary citation

Sung, M.W.,Hu, K.,Hurlimann, L.M.,Lees, J.A.,Fennell, K.F.,West, M.A.,Costales, C.,Rodrigues, A.D.,Zimmermann, I.,Dawson, R.J.P.,Liu, S.,Han, S.
Cyclosporine A sterically inhibits statin transport by solute carrier OATP1B1.
J.Biol.Chem., 301:108484-108484, 2025

PubMed Abstract: Members of the Organic Anion Transporter Polypeptides (OATP) are integral membrane proteins responsible for facilitating the transport of organic anions across the cell membrane. OATP1B1 (SLCO1B1), the prototypic OATP family member, is the most abundant uptake transporter in the liver and key mediator of the hepatic uptake and clearance of numerous endogenous and xenobiotic compounds. It serves as a locus of important drug-drug interactions, such as those between statins and cyclosporine A, and carries the potential to enable liver-targeting therapeutics. In this study, we report cryo-EM structures of OATP1B1 and its complexes with one of its statin substrates, atorvastatin, and an inhibitor, cyclosporine A. This structural analysis has yielded insights into the mechanisms underlying OATP1B1-mediated transport of statins and the inhibitory effect of cyclosporine A. These findings contribute to a better understanding of the molecular processes involved in drug transport and offer potential avenues for the development of targeted medications for liver-related conditions.

PubMed: 40199401
DOI: 10.1016/j.jbc.2025.108484

Experimental method

ELECTRON MICROSCOPY (3.15 Å)