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Structure and function of the melanocortin2 receptor accessory protein (MRAP)
Journal article   Open access   Peer reviewed

Structure and function of the melanocortin2 receptor accessory protein (MRAP)

Patricia M Hinkle and Julien A Sebag
Molecular and cellular endocrinology, Vol.300(1-2), pp.25-31
03/05/2009
DOI: 10.1016/j.mce.2008.10.041
PMID: 19028547
url
http://doi.org/10.1016/j.mce.2008.10.041View
Open Access

Abstract

The melanocortin2 (MC2), or ACTH receptor, requires MC2 receptor accessory protein (MRAP) for function, and individuals lacking MRAP are ACTH-resistant and glucocorticoid-deficient. MRAP facilitates trafficking of the MC2 receptor to the plasma membrane and is absolutely required for ACTH binding and stimulation of cAMP. MRAP, which contains a single transmembrane domain, has a unique structure, an antiparallel homodimer. It can be isolated from the plasma membrane in a complex with the MC2 receptor. A short sequence just aminoterminal to the transmembrane domain of MRAP is essential for dual topology, while the transmembrane region is not; both are necessary for function. Deletion or alanine-substitution of other aminoterminal regions yields MRAP mutants that promote surface expression of the MC2 receptor but not receptor signaling. These results identify two distinct actions of MRAP: to permit trafficking of the MC2 receptor, and to allow surface receptor binding and signaling.
MRAP ACTH GPCR Dual topology cAMP Melanocortin receptor

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