Mapping key regions of the RXFP2 low-density lipoprotein class-A module that are involved in signal activation

RCK Kong; RAD Bathgate; S Bruell; JD Wade; PR Gooley; EJ Petrie

Journal article

Mapping key regions of the RXFP2 low-density lipoprotein class-A module that are involved in signal activation

RCK Kong, RAD Bathgate, S Bruell, JD Wade, PR Gooley, EJ Petrie

Biochemistry | AMER CHEMICAL SOC | Published : 2014

DOI: 10.1021/bi500797d

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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University of Melbourne Researchers

Ross Bathgate Author

Paul Gooley Author

Related Projects (4)

Functional analysis of relaxin and INSL3 receptors

The peptide hormone relaxin is currently in clinical trials to treat acute heart failure. The related hormone INSL3 has important roles in f..

Determining modes of binding and activation of complex G-protein coupled receptor targets

The peptide hormones relaxin is currently in a Phase III trial for the treatment of heart failure. However the peptide is not a good drug as..

Functional analysis of relaxin and INSL3 receptors

The peptide hormone relaxin is currently in clinical trials to treat acute heart failure. The related hormone INSL3 has important roles in f..

Determining modes of binding and activation of complex G-protein coupled receptor targets

The peptide hormones relaxin is currently in a Phase III trial for the treatment of heart failure. However the peptide is not a good drug as..

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).