Learning from synthetic models: Differential binding of apolipoprotein A?I variants to components of the extracellular matrix.

ROSU, S. A; M. ALEJANDRA TRICERRI; LEANDRO TOLEDO; SANCHEZ DONOSO SUSANA; URBANO, BRUNO

Santiago

Simposio; Protein Biophysics at the End of the World; 2016

Facultad de Ciencias de la Universidad de Chile

Specific interactions among apolipoproteins and components of the extracellularmatrix particularly proteoglycans (PGs) seems key to regulate events associated toatherosclerosis. Moreover, the specific expression of different glycosamine glucans (GAGs) hasbeen reported to change in extent, position of sulfate substitution and composition dependingon age, differentiation, and pathological conditions. Human apolipoprotein A-I (apoA-I) doesnot bind GAGs but is supposed to inhibit the binding of oxidized LDL. Our previous resultsindicate that instead apoA-I binding to heparin is elicited under acidic pH or in a naturalamyloidogenic mutant with a single amino acid substitution (Arg173Pro), indicating thatcharge could play a key role in this interaction.In order to further study this protein-GAG interaction we built model polymers withdifferent ratio of sulfated-to hydroxilated monomers and studied binding by fluorescentlylabeled apoA-I or Arg173Pro. Results show that binding of both proteins is higher in thepolymers containing higher sulfate ratio, and that Arg173Pro binds with higher affinity to these model of matrices.We conclude that charge and chemical composition of the extra cellular matrix couldmediate protein binding to GAGs and as a consequence to alter the delicate equilibrium ofprotein function.