A distinct concerted mechanism of structural dynamism defines activity of human serine protease HtrA3.

ABSTRACT: Human HtrA3 (high-temperature requirement protease A3) is a trimeric multitasking propapoptotic serine protease associated with critical cellular functions and pathogenicity. Implicated in diseases including cancer and pre-eclampsia, its role as a tumor suppressor and potential therapeutic target cannot be ignored. Therefore, elucidating its mode of activation and regulatory switch becomes indispensable towards modulating its functions with desired effects for disease intervention. Using computational, biochemical and biophysical tools, we delineated the role of all domains, their combinations and the critical phenylalanine residues in regulating HtrA3 activity, oligomerization and specificity. Our findings underline the crucial roles of the N-terminus as well as the PDZ domain in oligomer

SUBMITTER: Acharya S 

PROVIDER: S-EPMC6993860 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature