Structure of the transmembrane signal initiation site of the relaxin-like factor (RLF/INSL3).
We have discovered the signal initiation structure of the relaxin-like factor and shown its function to be independent of the amino acid side chains in the contact region. Evidence presented in this article suggests that signal induction is a function of the peptide bond and that completion of the signaling contact is initiated by ligand binding to the leucine-rich repeat G-protein coupled receptor 8 (LGR8). The specific mode of binding forces certain peptide bonds into a signaling position. This observation implies that the receiving structures are equally nonspecific so that signaling should occur at any peptide bond of the receptor or the trans-membrane loop that is within reach of the signaling wires of the receptor-bound ligand. Our observations offer an explanation for ligand cross-talk as well as for the ability of some antibodies to elicit the biological response normally associated with a specific ligand.
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Avenue, Charleston, South Carolina 29425, USA.
Erika E
EE
Büllesbach
Christian
C
Schwabe
D002462:Cell Membrane / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021382:Protein Sorting Signals / Q000502:physiology*; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D007328:Insulin; C084797:Leydig insulin-like protein; D010446:Peptide Fragments; D021382:Protein Sorting Signals; D011506:Proteins; C472867:RXFP2 protein, human; D043562:Receptors, G-Protein-Coupled; D000242:Cyclic AMP