Organic Anion Transporting Polypeptides of the OATP/SLCO Superfamily: Identification of New Members in Nonmammalian Species, Comparative Modeling and a Potential Transport Mode |
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Authors: | Fabienne Meier-Abt Younes Mokrab Kenji Mizuguchi |
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Institution: | (1) Department of Biochemistry, University of Cambridge, Old Addenbrookes Site, 80 Tennis Court Road, Cambridge, CB1 1GA, United Kingdom;(2) Department of Applied Mathematics and Theoretical Physics, Centre for Mathematical Sciences, Wilberforce Road, Cambridge, CB3 0WA, United Kingdom |
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Abstract: | Organic anion-transporting polypeptides (human, OATPs; other animals, Oatps; gene symbol, SLCO/Slco) form a transport protein superfamily that mediates the translocation of amphipathic substrates across the plasma membrane
of animal cells. So far, OATPs/Oatps have been identified in human, rat and mouse tissues. In this study, we used bioinformatic
tools to detect new members of the OATP/SLCO superfamily in nonmammalian species and to build models for the three-dimensional structure of OATPs/Oatps. New OATP/SLCO superfamily members, some of which form distinct novel families, were identified in chicken, zebrafish, frog, fruit fly and
worm species. The lack of OATP/SLCO superfamily members in plants, yeast and bacteria suggests the emergence of an ancient Oatp protein in an early ancestor
of the animal kingdom. Structural models were generated for the representative members OATP1B3 and OATP2B1 based on the known
structures of the major facilitator superfamily of transport proteins. A model was also built for the large extracellular
region between transmembrane helices 9 and 10, following the identification of a novel homology with the Kazal-type serine
protease inhibitors. Along with the electrostatic potential and the conservation of key amino acid residues, we propose a
common transport mechanism for all OATPs/Oatps, whereby substrates are translocated through a central, positively charged
pore in a rocker-switch type of mechanism. Several amino acid residues were identified that may play crucial roles in the
proposed transport mechanism.
Electronic Supplementary Material Electronic Supplementary material is available for this article at
and accessible for authorised users. |
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Keywords: | Organic anion-transporting polypeptide (OATP) Phylogeny Structural model Transport mode |
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