Mouse relaxin: synthesis and biological activity of the first relaxin with an unusual crosslinking pattern.
According to a recently published cDNA sequence, mouse relaxin has an extra amino acid in the C-terminal end of the A chain and thus an interchain loop consisting of 25 amino acids instead of the usual 24-membered ring. Because of the restrictive disulfide link arrangement the extra residue can be expected to cause a loop out in the C-terminal alpha-helix. We have chemically synthesized authentic mouse relaxin as well as an analog without the additional A chain residue and found that the native hormone, although active, was inferior to its insulin-like analog. This result is in harmony with our previous study which suggests that the surface of relaxin represented by the C-terminal helix of the A chain is positioned opposite to the surface that contains the receptor interaction site and therefore is less sensitive to modifications.
Büllesbach
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Department of Biochemistry & Molecular Biology, Medical University of South Carolina, Charleston 29425.
Schwabe
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D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001681:Biological Assay; D001921:Brain / Q000378:metabolism; D002942:Circular Dichroism; D004220:Disulfides / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide / Q000378:metabolism; D012065:Relaxin / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology*; D017386:Sequence Homology, Amino Acid
D000596:Amino Acids; D004220:Disulfides; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; C033395:relaxin receptors; D012065:Relaxin