Deng, F. Y. & Bae, Y. H. Bile acid transporter-mediated oral drug delivery. J. Control. Release 327, 100–116 (2020).
Beaudoin, J. J., Brouwer, K. L. R. & Malinen, M. M. Novel insights into the organic solute transporter alpha/beta, OSTα/β: from the bench to the bedside. Pharmacol. Therapeut. https://doi.org/10.1016/j.pharmthera.2020.107542 (2020).
Ballatori, N., Christian, W. V., Wheeler, S. G. & Hammond, C. L. The heteromeric organic solute transporter, OSTα-OSTβ/SLC51: a transporter for steroid-derived molecules. Mol. Aspects Med. 34, 683–692 (2013).
Gao, E. et al. Organic solute transporter alpha deficiency: a disorder with cholestasis, liver fibrosis, and congenital diarrhea. Hepatology 71, 1879–1882 (2020).
Sultan, M. et al. Organic solute transporter-beta (SLC51B) deficiency in two brothers with congenital diarrhea and features of cholestasis. Hepatology 68, 590–598 (2018).
Collins, S. L., Stine, J. C., Bisanz, J. E., Okafor, C. D. & Patterson, A. D. Bile acids and the gut microbiota: metabolic interactions and impacts on disease. Nat. Rev. Microbiol. 21, 236–247 (2023).
Fleishman, J. S. & Kumar, S. Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets. Signal Transduct. Tar. https://doi.org/10.1038/s41392-024-01811-6 (2024).
Fang, F. et al. Neurosteroid transport by the organic solute transporter OSTα-OSTβ. J. Neurochem. 115, 220–233 (2010).
Boyer, J. L. & Soroka, C. J. Bile formation and secretion: an update. J. Hepatol. 75, 190–201 (2021).
Ferrebee, C. B. et al. Organic solute transporter α-β protects ileal enterocytes from bile acid-induced injury. Cell Mol. Gastroenter. 5, 499–522 (2018).
Goutam, K., Ielasi, F. S., Pardon, E., Steyaert, J. & Reyes, N. Structural basis of sodium-dependent bile salt uptake into the liver. Nature 606, 1015 (2022).
Liu, H. T. et al. Structure of human NTCP reveals the basis of recognition and sodium-driven transport of bile salts into the liver. Cell Res. 32, 773–776 (2022).
Shionoya, K. et al. Structural basis for hepatitis B virus restriction by a viral receptor homologue. Nat. Commun. 15, 9241 (2024).
Asami, J. et al. Structure of the bile acid transporter and HBV receptor NTCP. Nature 606, 1021–1026 (2022).
Liu, H. et al. Structure of antiviral drug bulevirtide bound to hepatitis B and D virus receptor protein NTCP. Nat. Commun. 15, 2476 (2024).
Hu, N. J., Iwata, S., Cameron, A. D. & Drew, D. Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT. Nature 478, 408 (2011).
Zhou, X. M. et al. Structural basis of the alternating-access mechanism in a bile acid transporter. Nature 505, 569–573 (2014).
Dawson, P. A. et al. The heteromeric organic solute transporter alpha-beta, Ostalpha-Ostbeta, is an ileal basolateral bile acid transporter. J. Biol. Chem. 280, 6960–6968 (2005).
Varadi, M. et al. AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Res. 50, D439–D444 (2022).
van Kempen, M. et al. Fast and accurate protein structure search with Foldseek. Nat. Biotechnol. 42, 243–246 (2024).
Gyimesi, G. & Hediger, M. A. Systematic in silico discovery of novel solute carrier-like proteins from proteomes. PLoS ONE 17, e0271062 (2022).
Pugh, R. J. et al. Transmembrane Protein 184A is a receptor required for vascular smooth muscle cell responses to heparin. J. Biol. Chem. 291, 5326–5341 (2016).
Chapman, K. A. et al. Pathogenic variants in TMEM184B cause a neurodevelopmental syndrome associated with alteration of metabolic signaling. Am. J. Hum. Genet. 112, 2381–2401 (2025).
Bhattacharya, M. R. C. et al. TMEM184b promotes axon degeneration and neuromuscular junction maintenance. J. Neurosci. 36, 4681–4689 (2016).
Suga, T., Yamaguchi, H., Ogura, J. & Mano, N. Characterization of conjugated and unconjugated bile acid transport via human organic solute transporter alpha/beta. Biochim. Biophys. Acta Biomembr. 1861, 1023–1029 (2019).
Holm, L., Laiho, A., Toronen, P. & Salgado, M. DALI shines a light on remote homologs: one hundred discoveries. Protein Sci. 32, e4519 (2023).
Kanada, S., Takeguchi, Y., Murakami, M., Ihara, K. & Kouyama, T. Crystal structures of an O-like blue form and an anion-free yellow form of pharaonis halorhodopsin. J. Mol. Biol. 413, 162–176 (2011).
Ballatori, N. Biology of a novel organic solute and steroid transporter, OSTalpha-OSTbeta. Exp. Biol. Med. 230, 689–698 (2005).
McCarthy, A. E., Yoshioka, C. & Mansoor, S. E. Full-length P2XStructures reveal how palmitoylation prevents channel desensitization. Cell 179, 659 (2019).
Drew, D., North, R. A., Nagarathinam, K. & Tanabe, M. Structures and general transport mechanisms by the Major Facilitator Superfamily (MFS). Chem. Rev. 121, 5289–5335 (2021).
Deng, D. et al. Crystal structure of the human glucose transporter GLUT1. Nature 510, 121–125 (2014).
Zeng, Y. C. et al. Structural basis of promiscuous substrate transport by Organic Cation Transporter 1. Nat. Commun. 14, 6374 (2023).
Varadi, M. et al. AlphaFold protein structure database in 2024: providing structure coverage for over 214 million protein sequences. Nucleic Acids Res. 52, D368–D375 (2024).
Padan, E. & Michel, H. NhaA: a unique structural fold of secondary active transporters. Isr. J. Chem. 55, 1233–1239 (2015).
Sakuragi, T. & Nagata, S. Regulation of phospholipid distribution in the lipid bilayer by flippases and scramblases (Apr 2023, 10.1038/s41580-02300604-z). Nat. Rev. Mol. Cell Bio. 24, 597–597 (2023).
Bushell, K. S. R. et al. The structural basis of lipid scrambling and inactivation in the endoplasmic reticulum scramblase TMEM16K. Nat. Commun. 10, 3956 (2019).
Sakuragi, T. et al. The tertiary structure of the human Xkr8-Basigin complex that scrambles phospholipids at plasma membranes. Nat. Struct. Mol. Biol. 28, 825 (2021).
Kasimova, M. A., Lindahl, E. & Delemotte, L. Determining the molecular basis of voltage sensitivity in membrane proteins. J. Gen. Physiol. 150, 1444–1458 (2018).
English, N. J. & Waldron, C. J. Perspectives on external electric fields in molecular simulation: progress, prospects and challenges. Phys. Chem. Chem. Phys. 17, 12407–12440 (2015).
Wang, W., Seward, D. J., Li, L., Boyer, J. L. & Ballatori, N. Expression cloning of two genes that together mediate organic solute and steroid transport in the liver of a marine vertebrate. Proc. Natl Acad. Sci. USA 98, 9431–9436 (2001).
Ballatori, N. et al. OSTalpha-OSTbeta: a major basolateral bile acid and steroid transporter in human intestinal, renal, and biliary epithelia. Hepatology 42, 1270–1279 (2005).
Yan, R., Zhao, X., Lei, J. & Zhou, Q. Structure of the human LAT1-4F2hc heteromeric amino acid transporter complex. Nature 568, 127–130 (2019).
Maxfield, F. R. & Wustner, D. Intracellular cholesterol transport. J. Clin. Invest. 110, 891–898 (2002).
Lu, Y. et al. Characterization of a novel organic solute transporter homologue from Clonorchis sinensis. PLoS Negl. Trop. Dis. 12, e0006459 (2018).
Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017).
Malinen, M. M., Ali, I., Bezencon, J., Beaudoin, J. J. & Brouwer, K. L. R. Organic solute transporter OSTalpha/beta is overexpressed in nonalcoholic steatohepatitis and modulated by drugs associated with liver injury. Am. J. Physiol. Gastrointest. Liver Physiol. 314, G597–G609 (2018).
Schott-Verdugo, S. & Gohlke, H. PACKMOL-Memgen: a simple-to-use, generalized workflow for membrane-protein-lipid-bilayer system building. J. Chem. Inf. Model. 59, 2522–2528 (2019).
Tian, C. et al. ff19SB: amino-acid-specific protein backbone parameters trained against quantum mechanics energy surfaces in solution. J. Chem. Theory Comput. 16, 528–552 (2020).
Dickson, C. J., Walker, R. C. & Gould, I. R. Lipid21: complex lipid membrane simulations with AMBER. J. Chem. Theory Comput. 18, 1726–1736 (2022).
He, X., Man, V. H., Yang, W., Lee, T. S. & Wang, J. A fast and high-quality charge model for the next generation general AMBER force field. J. Chem. Phys. 153, 114502 (2020).
Alenaizan, A., Burns, L. A. & Sherrill, C. D. Python implementation of the restrained electrostatic potential charge model. Int. J. Quantum Chem. 120, e26035 (2020).
Olsson, M. H. M., Søndergaard, C. R., Rostkowski, M. & Jensen, J. H. PROPKA3: consistent treatment of internal and surface residues in empirical pKa predictions. J. Chem. Theory Comput. 7, 525–537 (2011).
Lu, S. et al. Activation pathway of a G protein-coupled receptor uncovers conformational intermediates as targets for allosteric drug design. Nat. Commun. 12, 4721 (2021).
He, X. et al. Conformational selection mechanism provides structural insights into the optimization of APC-Asef inhibitors. Molecules https://doi.org/10.3390/molecules26040962 (2021).
Salomon-Ferrer, R., Götz, A. W., Poole, D., Le Grand, S. & Walker, R. C. Routine microsecond molecular dynamics simulations with AMBER on GPUs. 2. explicit solvent particle mesh Ewald. J. Chem. Theory Comput. 9, 3878–3888 (2013).
Roe, D. R. & Cheatham, T. E. III. PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data. J. Chem. Theory Comput. 9, 3084–3095 (2013).
He, X. Simulation files for Ostα/β. Zenodo https://doi.org/10.5281/zenodo.17656875 (2025).
