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The A-chain of the ...
The A-chain of the human relaxin family peptides has distinct roles in the binding and activation of the different relaxin family peptide receptors
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Hossain, M. Akhter (författare)
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- Rosengren, Johan (författare)
- Högskolan i Kalmar,Naturvetenskapliga institutionen
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- Haugaard-Kedström (published under the name Haugaard-Jönsson), Linda M. (författare)
- Högskolan i Kalmar,Naturvetenskapliga institutionen
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Zhang, Suode (författare)
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Layfield, Sharon (författare)
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Ferraro, Tania (författare)
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Daly, Norelle L. (författare)
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Tregear, Geoffrey W. (författare)
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Wade, John D. (författare)
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Bathgate, Ross A.D. (författare)
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(creator_code:org_t)
- 2008
- 2008
- Engelska.
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 283:25, s. 17287-17297
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The relaxin peptides are a family of hormones that share a structural fold characterized by two chains, A and B, that are cross-braced by three disulfide bonds. Relaxins signal through two different classes of G-protein-coupled receptors (GPCRs), leucine-rich repeat-containing GPCRs LGR7 and LGR8 together with GPCR135 and GPCR142, now referred to as the relaxin family peptide (RXFP) receptors 1-4, respectively. Although key binding residues have been identified in the B-chain of the relaxin peptides, the role of the A-chain in their activity is currently unknown. A recent study showed that INSL3 can be truncated at the N terminus of its A-chain by up to 9 residues without affecting the binding affinity to its receptor RXFP2 while becoming a high affinity antagonist. This suggests that the N terminus of the INSL3 A-chain contains residues essential for RXFP2 activation. In this study, we have synthesized A-chain truncated human relaxin-2 and -3 (H2 and H3) relaxin peptides, characterized their structure by both CD and NMR spectroscopy, and tested their binding and cAMP activities on RXFP1, RXFP2, and RXFP3. In stark contrast to INSL3, A-chain-truncated H2 relaxin peptides lost RXFP1 and RXFP2 binding affinity and concurrently cAMP-stimulatory activity. H3 relaxin A-chain-truncated peptides displayed similar properties on RXFP1, highlighting a similar binding mechanism for H2 and H3 relaxin. In contrast, A-chain-truncated H3 relaxin peptides showed identical activity on RXFP3, highlighting that the B-chain is the sole determinant of the H3 relaxin-RXFP3 interaction. Our results provide new insights into the action of relaxins and demonstrate that the role of the A-chain for relaxin activity is both peptide- and receptor-dependent.
Ämnesord
- NATURVETENSKAP -- Kemi -- Organisk kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences -- Organic Chemistry (hsv//eng)
Nyckelord
- Organic chemistry
- Organisk kemi
- Organisk kemi
- Organic Chemistry
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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