Journal article

Mapping Key Regions of the RXFP2 Low-Density Lipoprotein Class-A Module That Are Involved in Signal Activation

Roy CK Kong, Ross AD Bathgate, Shoni Bruell, John D Wade, Paul R Gooley, Emma J Petrie

BIOCHEMISTRY | AMER CHEMICAL SOC | Published : 2014

Abstract

The peptide hormone INSL3 and its receptor, RXFP2, have co-evolved alongside relaxin and its receptor, RXFP1. Both RXFP1 and RXFP2 are G protein-coupled receptors (GPCRs) containing the hallmark seven transmembrane helices in addition to a distinct ectodomain of leucine-rich repeats (LRRs) and a single low-density lipoprotein class-A (LDLa) module at the N-terminus. RXFP1 and RXFP2 are the only mammalian GPCRs known to contain an LDLa, and its removal does not perturb primary ligand binding to the LRRs; however, signaling is abolished. This presents a general mechanism whereby ligand binding induces a conformational change in the receptor to position the LDLa to elicit a signal response. Alt..

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Grants

Awarded by National Health and Medical Research Council (NHMRC) of Australia


Funding Acknowledgements

This research was supported by National Health and Medical Research Council (NHMRC) of Australia Project Grants 628427 and 1043750 (R.A.D.B. and P.R.G.) and by the Victorian Government Operational Infrastructure Support Program. Instrument funding by the State of Victoria, ARC-LIEF, and the Rowden White Foundation. R.A.D.B. and J.D.W. are recipients of an NHMRC Research Fellowship. R.C.K.K. is a recipient of a University of Melbourne International Research Scholarship and a University of Melbourne Fee Remission Scholarship. E.J.P. is a recipient of a Melbourne Research Fellowship (Career Interruptions).