Structure and function of cross-class complexes of G protein- coupled secretin and angiotensin 1a receptors

UM > Faculty of Arts and Humanities > DEPARTMENT OF CHINESE LANGUAGE AND LITERATURE

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	Structure and function of cross-class complexes of G protein- coupled secretin and angiotensin 1a receptors
	Harikumar, K; Augustine, ML; Chow, BK; Lee, T. O.; Miller, LJ
	2016-06-11
Source Publication	Journal of Biological Chemistry
ISSN	1083-351X
Pages	0-0
Abstract	Complexes of secretin (SecR) and angiotensin 1a (Atr1a) receptors have been proposed to be functionally important in osmoregulation, providing explanation for overlapping and interdependent functions of hormones that bind and activate different classes of GPCRs. However, the nature of these cross-class complexes has not been well characterized and their signaling properties have not been systematically explored. We now use competitive inhibition of receptor BRET and bimolecular fluorescence complementation to establish the dominant functionally-important state as a symmetrical homo-dimeric form of SecR decorated by monomeric Atr1a, interacting through lipid-exposed faces of Atr1a TM1 and TM4. Conditions increasing prevalence of this complex exhibited negative allosteric modulatory impact on secretin-stimulated cAMP responses at SecR. In contrast, activating Atr1a with full agonist in such a complex exhibited a positive allosteric modulatory impact on the same signaling event. This modulation was functionally biased, with secretin-stimulated calcium responses unaffected, while angiotensin-stimulated calcium responses through the complex were reduced or absent. Further supporting this interpretation, Atr1a with mutations of lipid-exposed faces of TM1 and TM4 that did not affect it
Keyword	secretin receptor G-protein coupled receptor dimerization
Language	英語English
The Source to Article	PB_Publication
PUB ID	19406
Document Type	Journal article
Collection	DEPARTMENT OF CHINESE LANGUAGE AND LITERATURE
Recommended Citation GB/T 7714	Harikumar, K,Augustine, ML,Chow, BK,et al. Structure and function of cross-class complexes of G protein- coupled secretin and angiotensin 1a receptors[J]. Journal of Biological Chemistry, 2016, 0-0.
APA	Harikumar, K., Augustine, ML., Chow, BK., Lee, T. O.., & Miller, LJ (2016). Structure and function of cross-class complexes of G protein- coupled secretin and angiotensin 1a receptors. Journal of Biological Chemistry, 0-0.
MLA	Harikumar, K,et al."Structure and function of cross-class complexes of G protein- coupled secretin and angiotensin 1a receptors".Journal of Biological Chemistry (2016):0-0.

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