Discerning the Mechanism of Action of HtrA4: a Serine Protease Implicated in the Cell Death Pathway.

Discerning the Mechanism of Action of HtrA4: a Serine Protease Implicated in the Cell Death Pathway. Biochem J. 2019 Apr 29;: Authors: Kummari R, Dutta S, Chaganti LK, Bose K Abstract High-temperature requirement protease A4 (HtrA4) is a secretary serine protease whose expression is up-regulated in pre-eclampsia (PE) and hence is a possible biomarker of PE. It has also been altered in cancers such as glioblastoma, breast carcinoma, and prostate cancer making it an emerging therapeutic target. Among the human HtrAs, HtrA4 is the least characterized protease pertaining to both structure as well as its functions. Although the members of human HtrA family share a significant structural and functional conservation, subtle structural changes have been associated with certain distinct functional requirements. Therefore, intricate dissection of HtrA4 structural and functional properties becomes imperative to understand its role in various biological and pathophysiological processes. Here, using inter-disciplinary approaches including in silico, biochemical and biophysical studies, we have done a domain-wise dissection of HtrA4 to delineate the roles of the domains in regulating oligomerization, stability, protease activity, and specificity. Our findings distinctly demonstrate the importance of the N-terminal region in oligomerization, stability and hence the formation of a functional enzyme. In silico structural comparison of HtrA4 with othe...
Source: The Biochemical Journal - Category: Biochemistry Authors: Tags: Biochem J Source Type: research