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OCTs, OATs, and OCTNs: structure and function of the polyspecific organic ion transporters of the SLC22 family

  • The SLC22 protein family includes more than 30 different proteins that operate as transporters for organic cations (OCTs), organic cations and zwitterions (OCTNs) or organic anions (OATs). These transporters play a pivotal role in the secretion of organic ions in kidney and liver. Furthermore, they contribute to the homeostasis of organic ions in several other tissues such as brain, placenta, intestine, and lung. Substrates include not only endogenous compounds such as monoamine neurotransmitters, choline, carnitine, α-ketoglutarate, urate, or steroid hormones, but also a broad spectrum of therapeutic drugs. Therefore, they control the bioavailability of many drugs and are responsible for several side effects or drug–drug interactions. SLC22 proteins are polyspecific transporters as they are able to transport structurally different compounds. All SLC22 proteins share a common membrane topology with 12 α-helical transmembrane domains. Mutational analyses and homology modeling of the steric structure of the proteins led to the conclusion that they possess a large cleft that is accessible from the aqueous phase. Located within this cleft is an inner cavity containing different interaction sites for different substrates. During the transport cycle the transporter undergoes conformational changes including an outward-open conformation, a transient occluded state and an inward-open conformation.

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Metadaten
Document Type:Article
Language:English
Parent Title (English):WIREs Membr Transp Signal (Wiley Interdisciplinary Reviews: Membrane Transport and Signaling)
Volume:3
Issue:1
First Page:1
Last Page:13
ISSN:2190-460X
DOI:https://doi.org/10.1002/wmts.100
Publisher:Wiley
Date of first publication:2013/12/18
Departments, institutes and facilities:Fachbereich Angewandte Naturwissenschaften
Institut für funktionale Gen-Analytik (IfGA)
Dewey Decimal Classification (DDC):500 Naturwissenschaften und Mathematik / 570 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Entry in this database:2015/04/02