Organic anion transporting polypeptides of the OATP/SLCO superfamily: Identification of new members in nonmammalian species, comparative modeling and a potential transport mode

Fabienne Meier-Abt, Younes Mokrab, Kenji Mizuguchi

Research output: Contribution to journalArticle

92 Citations (Scopus)

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 rockerswitch type of mechanism. Several amino acid residues were identified that may play crucial roles in the proposed transport mechanism.

Original languageEnglish
Pages (from-to)213-227
Number of pages15
JournalJournal of Membrane Biology
Volume208
Issue number3
DOIs
Publication statusPublished - Jan 2006
Externally publishedYes

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Anions
Peptides
Carrier Proteins
Amino Acids
Serine Proteinase Inhibitors
Structural Models
Zebrafish
Computational Biology
Static Electricity
Diptera
Anura
Chickens
Fruit
Yeasts
Cell Membrane
Bacteria
Genes
Proteins

Keywords

  • Organic anion-transporting polypeptide (OATP)
  • Phylogeny
  • Structural model
  • Transport mode

ASJC Scopus subject areas

  • Biophysics
  • Cell Biology
  • Physiology

Cite this

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