INVESTIGADORES
CHEHIN Rosana Nieves
congresos y reuniones científicas
Título:
Prediction of heparin binding sites on GAPDH
Autor/es:
TORRES BUGEAU, CLARISA; AVILA, CÉSAR; CHEHÍN ROSANA
Lugar:
Córdoba
Reunión:
Congreso; 2do Congreso Argentino de Bioinformática y Biología Computacional; 2011
Institución organizadora:
Sociedad Argentina de Bioinformática y Biología Computacional
Resumen:
Background
Lewy bodies and Lewy neuritis, neuropathological characteristics of Parkinsons disease,
are mainly made by filamentous assemblies of α-synuclein. However, glycosaminoglycans
(GAGs) along with other proteins like tau and Glyceraldehyde-3-phosphate
dehydrogenase (GAPDH) are routinely found associated with these amyloid deposits. It
has been suggested that GAPDH:GAGs interaction may play a key role in the formation of
Lewy´s bodies and it must be considered as main actors in Parkinsons disease and other
diseases involving α-synuclein aggregates. Indeed, it has been demonstrated that
heparin is able to trigger the GAPDH amyloid fibrils formation which in turn can also
induce a cross-seeding effect on the fibrillation of α-synuclein.
Results
Herein, we conducted an in silico search for heparin binding sites on GAPDH aided with
the program AutoDock. Because of the high charge density and the weak surface
complementarity of the sulfated sugar chain, prediction of heparin binding sites on
protein presents a challenging task for computational docking. We developed a protocol
that was able to successfully reproduce heparin binding sites on thrombin light chain and
acidic and basic fibroblast growth factor, three proteins for which structures of their
complexes with heparin are available. This procedure was then used to predict the
heparin binding site on GAPDH. The results indicate that positively charged residues play
a critical role in the interaction with the sulfate and carboxylate groups of the GAG chain.
Conclusions
Given the importance of protein-glycosaminoglycan interactions, the identification of
protein sequences that interact specifically with heparin could shed light on the
mechanism of protein amyloidogenesis.