INVESTIGADORES
AVILA Cesar Luis
congresos y reuniones científicas
Título:
Molecular dynamics simulations of the interaction between glyceraldehyde-3-phospate dehydrogenase and lipid bilayers
Autor/es:
AVILA, C L GONZALEZ-NILO, D DE LAS RIVAS, J MORERO, RD CHEHIN, R
Lugar:
Montevideo, Uruguay
Reunión:
Congreso; IV International Conference of Biological Physics; 2007
Resumen:
Membrane fusion is an ubiquitous event in cellular life and development. Despite the huge effort spent trying to elucidate the process, the molecular mechanisms which drive the membrane fusion, remains still unclear. Lipids membranes do not fuse spontaneously and thus, the process requires energy and “catalyzers” which help to overcome barriers that maintain the membrane integrity. The best studied “membrane fusion catalyzers” are the divalent cations, like calcium, and specific proteins related to virus infection and intracellular trafficking. In most of them, a conserved motif is recognized as responsible of the protein fusogenic activity, the so called “fusion peptide”. It is widely accepted that the fusion peptides cause the local destabilization of the lipid bilayer required to catalyze fusion. Novel fusogenic activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH),a globular cytoplasmic dehydrogenase was detected in our laboratory. This is an abundant cell protein with a pivotal role in energy production but also with a number of diverse activities unrelated to its glycolytic function. Careful sequence and structure analyses using bioinformatics techniques were performed in order to find any conserved linear or structural motif which resembles the fusogenic peptides found in viruses and other fusogenic systems. But, GAPDH is structurally unrelated with the previously described fusogenic proteins, suggesting that its activity could be described by novel mechanisms. Our structure and charge distribution studies on GAPDH showed that the protein has a characteristic deep positive crevice. Previous conformational studies with GAPDH and membranes showed that the protein would bind to the bilayer with its deep positive crevice facing the membrane. We proposed that this would then induce the generation of local membrane disorder which is indispensable to the membrane fusion event. To provide insight into these critical, experimentally unresolved questions, we performed large-scale molecular dynamics simulations to study the membrane response upon binding of GAPDH to the lipid bilayers.Understanding the molecular events that occur in cell membranes upon binding of fusogenic proteins represent an intriguing challenge and bioinformatics techniques showed to be a powerful tool in this area.