title: Structural modeling of the pro-ocytocin-neurophysin precursor.
abstract: The hormonal precursor pro-ocytocin-neurophysin is activated by selective cleavage at Arg2-Ala13, producing mature ocytocin and neurophysin. To understand the cleavage mechanism better, and in particular the recognition of the cleavage site, it is necessary to characterize the three-dimensional structure of the precursor molecule. Here we combine a variety of experimental data with molecular modeling and dynamics calculations to derive possible precursor conformations. In the models obtained, the N-terminus of the precursor, corresponding to the ocytocin segment, is hydrogen bonded in a pocket of the neurophysin moiety in a similar manner to a crystallographically obtained non-covalent complex between the two molecules. The calculations suggest that although the ocytocin segment is relatively flexible, it adopts a stable, broad loop structure in the vicinity of the cleavage region, which may constitute the structural element recognized by the cleaving enzyme. The calculations also suggest a possible widening of the distance between the two neurophysin domains in the precursor relative to that in the non-covalent neurophysin-ocytocin complex.
authors.affiliation: Section de Biophysique des Protéines et Membranes, CEA/Saclay, Gif-sur-Yvette, France.
authors.forename: B
authors.initials: B
authors.lastname: Velikson
authors.forename: P
authors.initials: P
authors.lastname: Cohen
authors.forename: M
authors.initials: M
authors.lastname: Rholam
authors.forename: J P
authors.initials: JP
authors.lastname: Rose
authors.forename: B C
authors.initials: BC
authors.lastname: Wang
authors.forename: J C
authors.initials: JC
authors.lastname: Smith
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003198:Computer Simulation; D003460:Crystallization; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009481:Neurophysins / Q000737:chemistry* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D010121:Oxytocin / Q000737:chemistry* / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D011498:Protein Precursors / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D004220:Disulfides; D009481:Neurophysins; D010446:Peptide Fragments; D011498:Protein Precursors; D010121:Oxytocin