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.