Distinct but overlapping binding sites of agonist and antagonist at the relaxin family peptide 3 (RXFP3) receptor

LLL Wong; DJ Scott; MA Hossain; QK Kaas; J Rosengren; RAD Bathgate

Journal article

Distinct but overlapping binding sites of agonist and antagonist at the relaxin family peptide 3 (RXFP3) receptor

LLL Wong, DJ Scott, MA Hossain, QK Kaas, J Rosengren, RAD Bathgate

Journal of Biological Chemistry | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2018

DOI: 10.1074/jbc.RA118.002645

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Abstract

The relaxin-3 neuropeptide activates the relaxin family peptide 3 (RXFP3) receptor to modulate stress, appetite, and cognition. RXFP3 shows promise as a target for treating neurological disorders, but realization of its clinical potential requires development of smaller RXFP3-specific drugs that can penetrate the blood– brain barrier. Designing such drugs is challenging and requires structural knowledge of agonist- and antagonist-binding modes. Here, we used structure–activity data for relaxin-3 and a peptide RXFP3 antagonist termed R3 B1–22R to guide receptor mutagenesis and develop models of their binding modes. RXFP3 residues were alanine-substituted individually and in combination and te..

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University of Melbourne Researchers

Daniel Scott Author

Akhter Hossain Author

Ross Bathgate Author

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Grants

Awarded by National Health and Medical Research Council

Funding Acknowledgements

[ "This work was supported by National Health and Medical Research Council (NHMRC) of Australia Project Grants 1066369 and 1065481 (to R. A. D. B. and K. J. R.) and the Victorian Government Operational Infrastructure Support Program. K. J. R. and R. A. D. B. are inventors on Australian Patent 2010904046 and United States patent application 13/821726, Modified Relaxin B Chain Peptides.", "Supported by the Melbourne Research Scholarship (MRS) and Melbourne International Fee Remission Scholarship (MIFRS).", "Supported by an NHMRC Dementia Fellowship.", "Supported by an Australian Research Council Future Fellowship.", "Supported by an NHMRC Research Fellowship." ]