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

Structure and function of the melanocortin2 receptor accessory protein (MRAP).
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DOI:
10.1016/j.mce.2008.10.041
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发表时间:
2009-03-05
影响因子:
4.1
通讯作者:
Sebag JA
Sebag JA
中科院分区:
医学2区
文献类型:
--
作者:
Hinkle PM;Sebag JA

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黑皮质素2(MC 21),或ACTH受体,需要MC 2受体辅助蛋白(MRAP)的功能,缺乏MRAP的个体是ACTH抵抗和糖皮质激素缺乏。MRAP促进MC 2受体向质膜的运输,并且是ACTH结合和cAMP刺激所绝对需要的。MRAP含有一个单一的跨膜结构域,具有独特的结构,即反平行同源二聚体。它可以与MC 2受体形成复合物从质膜分离。MRAP跨膜结构域氨基末端的短序列对于双重拓扑结构是必需的,而跨膜区不是;两者都是功能所必需的。其他氨基末端区域的缺失或丙氨酸取代产生促进MC 2受体的表面表达但不促进受体信号传导的MRAP突变体。这些结果确定了MRAP的两种不同作用:允许MC 2受体的运输,以及允许表面受体结合和信号传导。
The melanocortin2 (MC21), 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.
DOI: 10.1073/pnas.78.12.7431
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