IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Dissection of the in vivo interplay of molecular features determining protein evolution
Autor/es:
MARÍA-ROCÍO MEINI; GONZALEZ, L; TOMATIS, P E; A. J. VILA
Lugar:
Puerto Varas
Reunión:
Congreso; XII PABMB Congress; 2013
Resumen:
Protein evolution can be described
as a random walk on a sequence space where mutations are fixed based on their
impact on the organismal fitness. Fitness is a measure of the host organism´s
ability to reproduce faster at the conditions imposed by the environment. Two
of the major challenges in the field of protein evolution are to understand:
(1) how the structural, functional and biophysical features of proteins
determine molecular evolution, and (2) how mutations accumulate and impact in
these molecular features.The order in which mutations appear is not trivial,
since the effect of each mutation depends on the genetic background, a
phenomenon known as epitasis.
We have analyzed the molecular
features evinced by the accumulation of mutations in the evolutionary pathways
of a Metallo-β-lactamase, a Zn(II)-dependent enzyme able to provide antibiotic
resistance to pathogenic and opportunistic bacteria. We have been able to
assess the impact of four different mutations and their combinations in the
protein stability and function in the periplasmic space. This approach allows
us to fill the gap between the biochemical and biophysical features determined
in vitro in purified proteins, and the resistance conferred to bacteria, which
ultimately represents organismal fitness. We also found that epistatic
interactions in the evolutionary pathways can be accounted for by only three
molecular properties evaluated in
periplasma: catalytic efficiency, protein stability and enzyme activation
by binding of the essential Zn(II) cofactor in
vivo.