Reactivity of basic amino acid pairs in prohormone processing: model of pro-ocytocin/neurophysin processing domain.
Statistical analysis of several potential dibasic cleavage sites reveals differences in the distribution of basic doublets when the in vivo cleaved sites were compared to those which are not cleaved. Analysis of the substrate specificity of protease Kex2 towards the pro-ocytocin/neurophysin processing domain (pro-OT/Np(7-15) with altered basic pairs shows a cleavage efficiency order in accord with the statistical data. Structural analysis of these substrates indicates that each basic pair is associated with a local and specific conformational change. Thus, the in vivo cleavage hierarchy of dibasic sites is encoded by both the nature of basic pairs and the plasticity of proteolytic processing domains.
Lazar
Noureddine
N
Laboratoire de Biochimie des Signaux Régulateurs Cellulaires et Moléculaires, FRE 2621 CNRS, Université Paris6--Pierre et Marie Curie, 96 Boulevard Raspail, 75006 Paris, France.
Brakch
Noureddine
N
Panchal
Maï
M
Fahy
Christine
C
Rholam
Mohamed
M
D024361:Amino Acids, Basic / Q000032:analysis / Q000737:chemistry*; D002942:Circular Dichroism; D007700:Kinetics; D009481:Neurophysins / Q000737:chemistry* / Q000378:metabolism; D010121:Oxytocin / Q000737:chemistry* / Q000378:metabolism; D043484:Proprotein Convertases / Q000378:metabolism; D011498:Protein Precursors / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013379:Substrate Specificity
D024361:Amino Acids, Basic; D009481:Neurophysins; D011498:Protein Precursors; D010121:Oxytocin; D043484:Proprotein Convertases