title: Insights from bacterial subtilases into the mechanisms of intramolecular chaperone-mediated activation of furin.
abstract: Prokaryotic subtilisins and eukaryotic proprotein convertases (PCs) are two homologous protease subfamilies that belong to the larger ubiquitous super-family called subtilases. Members of the subtilase super-family are produced as zymogens wherein their propeptide domains function as dedicated intramolecular chaperones (IMCs) that facilitate correct folding and regulate precise activation of their cognate catalytic domains. The molecular and cellular determinants that modulate IMC-dependent folding and activation of PCs are poorly understood. In this chapter we review what we have learned from the folding and activation of prokaryotic subtilisin, discuss how this has molded our understanding of furin maturation, and foray into the concept of pH sensors, which may represent a paradigm that PCs (and possibly other IMC-dependent eukaryotic proteins) follow for regulating their biological functions using the pH gradient in the secretory pathway.
authors.affiliation: Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, OR 97229, USA. shindeu@ohsu.edu
authors.forename: Ujwal
authors.initials: U
authors.lastname: Shinde
authors.forename: Gary
authors.initials: G
authors.lastname: Thomas
mesh_terms: D001407:Bacillus; D001426:Bacterial Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D004792:Enzyme Precursors / Q000378:metabolism; D045683:Furin / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding; D017510:Protein Folding; D011499:Protein Processing, Post-Translational / Q000502:physiology; D055571:Secretory Pathway / Q000502:physiology*; D013381:Subtilisins / Q000378:metabolism* / Q000648:ultrastructure; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D004792:Enzyme Precursors; D018832:Molecular Chaperones; D013381:Subtilisins; D045683:Furin