Progerin–lamin A protein-protein interface (Progerin–Lamin A PPI)

The Progerin–lamin A protein-protein interface is a critical pathological target in the study of Hutchinson-Gilford Progeria Syndrome (HGPS), a rare genetic disorder characterized by premature aging. Progerin is a mutant, farnesylated form of the Lamin A protein (encoded by the LMNA gene) that lacks 50 amino acids due to a cryptic splicing event (UniProt P02545). This mutant protein accumulates at the nuclear envelope and interacts abnormally with wild-type Lamin A and other nuclear proteins, leading to severe structural defects such as nuclear blebbing and genomic instability (Lee et al., 2016, Nature Communications). By targeting the specific interface where progerin binds to lamin A, researchers aim to disrupt these toxic interactions and restore normal nuclear architecture. Small molecules like Progerinin (SLC-D011) have been identified to bind this interface, effectively displacing progerin and improving cellular phenotypes in HGPS models (Lee et al., 2016). This target is distinct from farnesyltransferase inhibitors, as it directly addresses the protein-protein interaction rather than the post-translational modification of progerin.

Other names

Progerin-LMNA interactionProgerin-Lamin A complexProgerin-Lamin A/C interface

Small molecule inhibition of the protein-protein interaction between mutant progerin and wild-type lamin A/C proteins to prevent dominant-negative structural disruption.