Journal article

Identification of Key Residues Essential for the Structural Fold and Receptor Selectivity within the A-chain of Human Gene-2 (H2) Relaxin

Linda J Chan, K Johan Rosengren, Sharon L Layfield, Ross AD Bathgate, Frances Separovic, Chrishan S Samuel, Mohammed A Hossain, John D Wade

JOURNAL OF BIOLOGICAL CHEMISTRY | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2012

Abstract

Human gene-2 (H2) relaxin is currently in Phase III clinical trials for the treatment of acute heart failure. It is a 53-amino acid insulin-like peptide comprising two chains and three disulfide bonds. It interacts with two of the relaxin family peptide (RXFP) receptors. Although its cognate receptor is RXFP1, it is also able to cross-react with RXFP2, the native receptor for a related peptide, insulin-like peptide 3. In order to understand the basis of this cross-reactivity, it is important to elucidate both binding and activation mechanisms of this peptide. The primary binding mechanism of this hormone has been extensively studied and well defined. H2 relaxin binds to the leucine-rich repe..

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Grants

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


Funding Acknowledgements

This research was funded by National Health and Medical Research Council (NHMRC) (Australia) Project Grants 508995 and 1023078 (to J. D. W., M. A. H., and R. A. D. B.). Studies at the Florey Neuroscience Institutes were supported by the Victorian Government's Operational Infrastructure Support Program.Recipient of Reid Trust and Florey Foundation Fellowships.