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Portrait of multifaceted transporter, the multidrug resistance-associated protein 1 (MRP1/ABCC1)

2006; Springer Science+Business Media; Volume: 453; Issue: 5 Linguagem: Inglês

10.1007/s00424-006-0160-8

1432-2013

Éva Bakos, László Homolya,

Pediatric Hepatobiliary Diseases and Treatments

MRP1 (ABCC1) is a peculiar member of the ABC transporter superfamily for several aspects. This protein has an unusually broad substrate specificity and is capable of transporting not only a wide variety of neutral hydrophobic compounds, like the MDR1/P-glycoprotein, but also facilitating the extrusion of numerous glutathione, glucuronate, and sulfate conjugates. The transport mechanism of MRP1 is also complex; a composite substrate-binding site permits both cooperativity and competition between various substrates. This versatility and the ubiquitous tissue distribution make this transporter suitable for contributing to various physiological functions, including defense against xenobiotics and endogenous toxic metabolites, leukotriene-mediated inflammatory responses, as well as protection from the toxic effect of oxidative stress. In this paper, we give an overview of the considerable amount of knowledge which has accumulated since the discovery of MRP1 in 1992. We place special emphasis on the structural features essential for function, our recent understanding of the transport mechanism, and the numerous assignments of this transporter.