The relaxin receptor (RXFP1) utilizes hydrophobic moieties on a signaling surface of its N-terminal low density lipoprotein class a module to mediate receptor activation

RCK Kong; EJ Petrie; B Mohanty; J Ling; JCY Lee; PR Gooley; RAD Bathgate

Journal article

The relaxin receptor (RXFP1) utilizes hydrophobic moieties on a signaling surface of its N-terminal low density lipoprotein class a module to mediate receptor activation

RCK Kong, EJ Petrie, B Mohanty, J Ling, JCY Lee, PR Gooley, RAD Bathgate

Journal of Biological Chemistry | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2013

DOI: 10.1074/jbc.M113.499640

Abstract

Background: Activation of the relaxin receptor RXFP1 is driven by the LDLa module at the RXFP1 N terminus. Results: LDLa residues Leu-7, Tyr-9, and Lys-17 all contribute to receptor activation via interactions involving their hydrophobic side chains. Conclusion: These interactions induce the active receptor conformation, suggesting a novel mode of GPCR activation. Significance: This novel mechanism of GPCR activation may lead to new drug development. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.

University of Melbourne Researchers

Paul Gooley Author

Ross Bathgate Author

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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..

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Grants

Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

This work was supported in part by National Health and Medical Research Council of Australia Project Grants 628427 and 1043750 (to R.A.D.B. and P.R.G.) and by the Victorian Government Operational Infrastructure Support Program.