Conformational Dynamics and Activation of Membrane-Associated Human Group IVA Cytosolic Phospholipase A₂ (cPLA₂).

ABSTRACT: Cytosolic phospholipase A₂ (cPLA₂) associates with membranes, where it hydrolyzes phospholipids containing arachidonic acid to initiate an inflammatory cascade. All-atom molecular dynamics simulations were employed to understand the activation process when cPLA₂ associates with the endoplasmic reticulum (ER) membrane of macrophages, where it acts. We found that membrane association causes the lid region of cPLA₂ to undergo a closed-to-open state transition that is accompanied by the sideways movement of loop 495-540, allowing the exposure of a cluster of lysine residues (K488, K541, K543, and K544), which are known to bind allosteric activator PIP₂ from the membrane. The active site of the open form of cPLA₂, containing cata

SUBMITTER: Braza MKE 

PROVIDER: S-EPMC12183713 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature