Conserved folding landscape of monomeric initiator caspases.

ABSTRACT: The apoptotic caspase subfamily evolved into two subfamilies-monomeric initiators and dimeric effectors; both subfamilies share a conserved caspase-hemoglobinase fold with a protease domain containing a large subunit and a small subunit. Sequence variations in the conserved caspase-hemoglobinase fold resulted in changes in oligomerization, enzyme specificity, and regulation, making caspases an excellent model for examining the mechanisms of molecular evolution in fine-tuning structure, function, and allosteric regulation. We examined the urea-induced equilibrium folding/unfolding of two initiator caspases, monomeric caspase-8 and cFLIP_L, over a broad pH range. Both proteins unfold by a three-state equilibrium mechanism that includes a partially folded intermediate. In addition,

SUBMITTER: Nag M 

PROVIDER: S-EPMC10074801 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature