Interactions of variants of human apolipoprotein A-I with biopolymeric model matrices. Effect of collagen and heparin.

Autor: Rosú SA; Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CONICET. Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Calle 60 y 120, La Plata, Buenos Aires, Argentina; Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina., Aguilar J; Laboratorio de Interacciones Macromoleculares (LIMM), Departamento de Polímeros, Facultad de Ciencias Químicas, Universidad de Concepción, Concepción, Chile., Urbano BF; Laboratorio de Interacciones Macromoleculares (LIMM), Departamento de Polímeros, Facultad de Ciencias Químicas, Universidad de Concepción, Concepción, Chile., Tarraga WA; Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Universidad Nacional de La Plata-CONICET, La Plata, Buenos Aires, Argentina., Ramella NA; Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CONICET. Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Calle 60 y 120, La Plata, Buenos Aires, Argentina; Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina., Longo GS; Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Universidad Nacional de La Plata-CONICET, La Plata, Buenos Aires, Argentina., Finarelli GS; Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CONICET. Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Calle 60 y 120, La Plata, Buenos Aires, Argentina., Sanchez Donoso SA; Laboratorio de Interacciones Macromoleculares (LIMM), Departamento de Polímeros, Facultad de Ciencias Químicas, Universidad de Concepción, Concepción, Chile. Electronic address: susanchez@udec.cl., Tricerri MA; Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CONICET. Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Calle 60 y 120, La Plata, Buenos Aires, Argentina; Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina. Electronic address: aletricerri@med.unlp.edu.ar.
Jazyk: angličtina
Zdroj: Archives of biochemistry and biophysics [Arch Biochem Biophys] 2023 Dec; Vol. 750, pp. 109805. Date of Electronic Publication: 2023 Oct 31.
DOI: 10.1016/j.abb.2023.109805
Abstrakt: Background: The extracellular matrix (ECM) is a complex tridimensional scaffold that actively participates in physiological and pathological events. The objective of this study was to test whether structural proteins of the ECM and glycosaminoglycans (GAGs) may favor the retention of human apolipoprotein A-I (apoA-I) variants associated with amyloidosis and atherosclerosis.
Methods: Biopolymeric matrices containing collagen type I (Col, a main macromolecular component of the ECM) with or without heparin (Hep, a model of GAGs) were constructed and characterized, and used to compare the binding of apoA-I having the native sequence (Wt) or Arg173Pro, a natural variant inducing cardiac amyloidosis. Protein binding was observed by fluorescence microscopy and unbound proteins quantified by a colorimetric assay.
Results: Both, Wt and Arg173Pro bound to the scaffolds containing Col, but the presence of Hep diminished the binding efficiency. Col-Hep matrices retained Arg173Pro more than the Wt. The retained protein was only partially removed from the matrices with saline solutions, indicating that electrostatic interactions may occur but are not the main driving force. Using in addition thermodynamic molecular simulations and size exclusion chromatography approaches, we suggest that the binding of apoA-I variants to the biopolymeric matrices is driven by many low affinity interactions.
Conclusions: Under this scenario Col-Hep scaffolds contribute to the binding of Arg173Pro, as a cooperative platform which could modify the native protein conformation affecting protein folding.
General Significance: We show that the composition of the ECM is key to the protein retention, and well characterized biosynthetic matrices offer an invaluable in vitro model to mimic the hallmark of pathologies with interstitial infiltration such as cardiac amyloidosis.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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