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Reproduction Abstracts (2014) 1 P315 | DOI: 10.1530/repabs.1.P315

University of Massachusetts Boston, Boston, Massachusetts, USA.


Organisms use protein hormones even when smaller molecules can trigger identical transduction paths. Why? Could residual peptides from hormone proteolysis extend the mechanisms of action of these hormones? Protein hormones are endocytosed by target cells and digested by cathepsins (A, B, C, D, F, H, L, O, X) acting sequentially as endosomes/lysosomes move centripetally. In silico prediction of multiple cathepsin action on each of 92 hormones usually leaves 3–24 residual peptides of 6–25 amino acids; post-translational modification maps suggest some predicted cleavages may be blocked in vivo so residual peptides may be even longer (the 30-residue hCGβ C-terminus may remain nearly intact). Stepwise application of cathepsins to hormones known to contain independently active peptides also suggests etiologies (cathepsins S and K release obestatin from GHrelin). Complete endosomal digestion of most protein hormones is unlikely so more secondary hormones (vasoinhibin from prolactin, preptin from IGFII) or peptides active in metabolically modulating cytoplasmic proteins in target cells are expected. To find transducer or modulator peptides and their cytoplasmic targets (peptide-motif-matched-proteins, PMMPs) BLASTp (1D matches) and LabelHash (3D matches) are applied; 1D matches with E<0.05 and 3D matches with P<0.01 for LRMSD for non-parent homologs are common with many located on PMMP surfaces. PMMPs used to seed network software (CytoScape, STRING) identify PMMP partners; peptide motif involvement in PMMP-partner binding is ascertained from known complex structures or docking software. Complexes that use peptide motifs dictate future bench tests for peptide actions. Present results suggest proteolytic peptides do extend protein hormone action mechanisms.

Volume 1

World Congress of Reproductive Biology 2014

Edinburgh, UK
02 Sep 2014 - 04 Sep 2014

World Congress of Reproductive Biology 

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