Structural Implications of H233L and H398P Mutations in Phospholipase Cζ: A Full-Atom Molecular Dynamics Study on Infertility-Associated Dysfunctions.

ABSTRACT: Phospholipase Cζ (PLCζ), a sperm-specific enzyme, plays a critical role in mammalian fertilization. Mutations in PLCζ have been linked to male infertility, as they impair its ability to trigger calcium (Ca²⁺) oscillations necessary for egg activation and embryo development. During fertilization, PLCζ is introduced into the egg, where it hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP₂) into inositol 1,4,5-trisphosphate and diacylglycerol, leading to Ca²⁺ release from the endoplasmic reticulum. Human infertility-associated mutations include H233L, H398P, and R553P, which disrupt PLCζ function. To elucidate the molecular consequences of the mutations, we employed full-atom molecular dynamics simulations to analyze structural perturbations and their impa

SUBMITTER: Hinostroza F 

PROVIDER: S-EPMC12111915 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature