The HCM - Linked Mutation Arg92Leu in TNNT2 Allosterically Alters the cTnC - cTnI Interface and Disrupts the PKA-mediated Regulation of Myofilament Relaxation.
Melissa L LynnJesus JimenezRomi L CastilloMatthew M KlassCatherine VasquezAnthony BaldoCyonna GibsonAnne M MurphyJil C TardiffPublished in: bioRxiv : the preprint server for biology (2023)
These data indicate that the early diastolic dysfunction observed in a subset of HCM is likely attributable to structural changes at the cTnC-cTnI interface that impair accessibility of PKA thereby blunting β-adrenergic responsiveness and identifying a potential molecular target for therapeutic intervention.