Influence of membrane composition on the amyloidogenic properties of glyceraldehyde-3-P-dehydrogenase

TORRES-BUGEAU, CLARISA MARÍA; AVILA, CÉSAR LUIS; CORTEZ, LEONARDO; MORERO, ROBERTO D; CHEHÍN, ROSANA

La Plata

Congreso; XXXVII Reunion Anual de la Sociedad Argentina de Biofisica; 2008

Protein misfolding and the subsequent aggregation is associated with various, often highly debilitating diseases, for which no sufficient cure is available yet. The number of pathologies associated to tissue deposition of amyloid fibrils in humans and animals dramatically increased in the last decade. The outstanding importance of protein self-aggregation in human and bovine diseases, support the extensive effort directed towards obtaining better understanding  of fibrils formation mechanism. Under in vitro solution conditions where the native state is destabilized, many proteins present an abnormal structure with a strong tendency to self-aggregation into a polymeric amyloid fibril structure. At present, it is accepted that the ability to form amyloid structures is not an unusual feature of the small number of proteins associated with these diseases but is, instead, a generic feature of any polypeptidic chain. The physicochemical basis of amyloid formation remains poorly understood. It was reported that PS as well as other acidic phospholipids can enhance protein fibril formation in vivo. In the present work, the influence of the lipid composition in the ability of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and alcohol dehydrogenase (ADH) to form amyloid aggregates was analyzed by fluorescence and infrared spectroscopy. The obtained results suggest that GAPDH could form amyloid aggregates without lag phase at pH 7.40 as well as pH 5.0. The presence of cholesterol and negative charge in the membranes increase the rate and amount of fibrils formation. However, an increment on the molar fraction of acidic lipids do not change the amount of fibrils formed. On the other hand, ADH can only form amyloid aggregates at pH 5.0. The present work could shed light on the molecular mechanism of the amyloid fibrils formation demonstrating the significant role that surfaces play in protein aggregation.