Remodeling of the interdomain allosteric linker upon membrane binding of CCTα pulls its active site close to the membrane surface.

ABSTRACT: The rate-limiting step in the biosynthesis of the major membrane phospholipid, phosphatidylcholine, is catalyzed by CTP:phosphocholine cytidylyltransferase (CCT), which is regulated by reversible membrane binding of a long amphipathic helix (domain M). The M domain communicates with the catalytic domain via a conserved ∼20-residue linker, essential for lipid activation of CCT. Previous analysis of this region (denoted as the αE_C/J) using MD simulations, cross-linking, mutagenesis, and solvent accessibility suggested that membrane binding of domain M promotes remodeling of the αE_C/J into a more compact structure that is required for enzyme activation. Here, using tryptophan fluorescence quenching, we show that the allosteric linker lies superficially on the membrane su

SUBMITTER: Knowles DG 

PROVIDER: S-EPMC6802524 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature