Work

Insights from Bacterial Subtilases into the Mechanisms of Intramolecular Chaperone-Mediated Activation of Furin

Year: 2011

Type: book-chapter

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.

Source: Methods in molecular biology

DOI: 10.1007/978-1-61779-204-5_4

Authors: Ujwal Shinde, Gary Thomas

Institutions: Oregon Health & Science University, Vollum Institute

Language: English

Topic: Protease and Inhibitor Mechanisms

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases

Awards: Role of PACS proteins in polycystin-2 trafficking and ADPKD, Regulation of TRAIL Induced Apoptosis in Cancer Cells, G2407511655, G526527174