Oligomeric assembly regulating mitochondrial HtrA2 function as examined by methyl-TROSY NMR.

ABSTRACT: Human High temperature requirement A2 (HtrA2) is a mitochondrial protease chaperone that plays an important role in cellular proteostasis and in regulating cell-signaling events, with aberrant HtrA2 function leading to neurodegeneration and parkinsonian phenotypes. Structural studies of the enzyme have established a trimeric architecture, comprising three identical protomers in which the active sites of each protease domain are sequestered to form a catalytically inactive complex. The mechanism by which enzyme function is regulated is not well understood. Using methyl transverse relaxation optimized spectroscopy (TROSY)-based solution NMR in concert with biochemical assays, a functional HtrA2 oligomerization/binding cycle has been established. In the absence of substrates, HtrA2 exchanges

SUBMITTER: Toyama Y 

PROVIDER: S-EPMC7980377 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature