PUBLICATION
Organic Anion Transporting Polypeptides of the OATP/SLCO Superfamily: Identification of New Members in Nonmammalian Species, Comparative Modeling and a Potential Transport Mode
- Authors
- Meier-Abt, F., Mokrab, Y., and Mizuguchi, K.
- ID
- ZDB-PUB-060508-4
- Date
- 2005
- Source
- The Journal of membrane biology 208(3): 213-227 (Journal)
- Registered Authors
- Keywords
- Organic anion-transporting polypeptide (OATP), Phylogeny, Structural model, Transport mode
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Binding Sites
- Biological Transport
- Computer Simulation
- Mammals
- Models, Biological*
- Models, Chemical*
- Models, Molecular*
- Molecular Sequence Data
- Organic Anion Transporters/chemistry*
- Organic Anion Transporters/metabolism*
- Protein Binding
- Species Specificity
- Structure-Activity Relationship
- PubMed
- 16648940 Full text @ J. Membr. Biol.
Citation
Meier-Abt, F., Mokrab, Y., and Mizuguchi, K. (2005) Organic Anion Transporting Polypeptides of the OATP/SLCO Superfamily: Identification of New Members in Nonmammalian Species, Comparative Modeling and a Potential Transport Mode. The Journal of membrane biology. 208(3):213-227.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping