The Roles of the A- and B-Chains of Human Relaxin-2 and -3 on Their Biological Activity

Author(s): Mohammed Akhter Hossain, John D. Wade.

Journal Name: Current Protein & Peptide Science

Volume 11 , Issue 8 , 2010

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Abstract:

Two members of the human insulin/relaxin superfamily, relaxins-2 and 3 (H2 and H3 respectively), are separated by nearly 75 years in terms of chronological identification but are both the subject of intense recent biological study. The physiological effects of H2 relaxin include vasodilatory, anti-inflammatory, extracellular matrix remodeling, and angiogenic and anti-ischemic. Because of its potent systemic and renal vasodilatory effects, it is currently undergoing phase III clinical trial for the treatment of acute heart failure. In contrast, H3 relaxin is a highly conserved neuropeptide that has rapidly emerged as an important regulator of homeostatic physiology and complex behaviors. Because of their immense clinical potential, an understanding of the structural features that control their functions is critical for rational drug design and development. The native receptor for H2 relaxin is RXFP1. It also strongly binds to the related receptor, RXFP2. The native receptor for H3 relaxin is the unrelated receptor, RXFP3; however, it also has high affinity for another related receptor, RXFP4. Interestingly, H3 relaxin also has a high affinity for RXFP1 and can interact with RXFP2 with a significantly lower affinity. H3 relaxin thus interacts with all four of the relaxin family receptors. Previous studies have shown that H2 and H3 relaxins interact with their receptors primarily using their B-chain specific residues. However, more recent studies suggest that the role of the respective A and B chains for their activity is both peptide- and receptor-dependent. This mini-review summarizes these recent findings on the structure-activity relationships of H2 and H3 relaxins.

Keywords: Relaxin, H2 relaxin, H3 relaxin, RXFP1, RXFP3, INSL3, vaodilatory, anti-inflammatory, extracellular matrix remodeling, A-chains, hydogen bonding, B-chains, alpha helicx, antagonist, N-terminus

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Article Details

VOLUME: 11
ISSUE: 8
Year: 2010
Page: [719 - 724]
Pages: 6
DOI: 10.2174/138920310794557736
Price: $58

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