Structural and functional characterization of the Pro64Ser leptin mutant: Implications for congenital leptin deficiency.

ABSTRACT: Congenital leptin deficiency or dysfunction is a form of monogenic childhood obesity. The disease is primarily caused by mutations in the LEP gene, which encodes for the expression of a hormone called leptin. The mutations typically impair leptin synthesis, secretion, or binding to the leptin receptor (LepR). The Pro64Ser mutation in leptin, despite not affecting the protein's stability or its binding affinity to the LepR, completely abolishes the protein's ability to mediate intracellular signaling via the LepR. To elucidate the mechanism underlying this signal inhibition and to further understand the mechanism of leptin-mediated LepR signal transduction, we performed extensive molecular dynamics simulations of both the wild-type and mutant (MT) leptins. Our simulations reveal that the Pr

SUBMITTER: Ngo BQ 

PROVIDER: S-EPMC12709403 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature