2FHW

Solution structure of human relaxin-3

Summary for 2FHW

• Entry DOI: 10.2210/pdb2fhw/pdb
• Descriptor: Relaxin 3 (Prorelaxin H3) (Insulin-like peptide INSL7) (Insulin-like peptide 7) (2 entities in total)
• Functional Keywords: insulin/relaxin super-family fold, signaling protein
• Cellular location: Secreted: Q8WXF3 Q8WXF3
• Total number of polymer chains: 2
• Total formula weight: 5513.43

Authors

Rosengren, K.J.,Craik, D.J. (deposition date: 2005-12-27, release date: 2006-01-24, Last modification date: 2022-03-09)

Primary citation

Rosengren, K.J.,Lin, F.,Bathgate, R.A.,Tregear, G.W.,Daly, N.L.,Wade, J.D.,Craik, D.J.
Solution structure and novel insights into the determinants of the receptor specificity of human relaxin-3.
J.Biol.Chem., 281:5845-5851, 2006

PubMed Abstract: Relaxin-3 is the most recently discovered member of the relaxin family of peptide hormones. In contrast to relaxin-1 and -2, whose main functions are associated with pregnancy, relaxin-3 is involved in neuropeptide signaling in the brain. Here, we report the solution structure of human relaxin-3, the first structure of a relaxin family member to be solved by NMR methods. Overall, relaxin-3 adopts an insulin-like fold, but the structure differs crucially from the crystal structure of human relaxin-2 near the B-chain terminus. In particular, the B-chain C terminus folds back, allowing Trp(B27) to interact with the hydrophobic core. This interaction partly blocks the conserved RXXXRXXI motif identified as a determinant for the interaction with the relaxin receptor LGR7 and may account for the lower affinity of relaxin-3 relative to relaxin for this receptor. This structural feature is likely important for the activation of its endogenous receptor, GPCR135.

PubMed: 16365033
DOI: 10.1074/jbc.M511210200

Experimental method

SOLUTION NMR