INVESTIGADORES
ROMAN Ernesto Andres
artículos
Título:
Frataxin from Psychromonas ingrahamii as a model to study stability modulation within the CyaY protein family
Autor/es:
ERNESTO A. ROMAN; SANTIAGO FARAJ; ALEXANDRA COUSIDO-SIAH; ANDRE MITSCHLER; ALBERTO PODJARNY; JAVIER SANTOS
Revista:
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
Editorial:
ELSEVIER SCIENCE BV
Referencias:
Lugar: Amsterdam; Año: 2013 vol. 1834 p. 1168 - 1180
ISSN:
1570-9639
Resumen:
Adaptation of life to low temperatures influences both protein stability
and flexibility. Thus, proteins from psychrophilic organisms are
excellent models to study relations between these properties. Here we
focused on frataxin from Psychromonas ingrahamii (pFXN), an
extreme psychrophilic sea ice bacterium that can grow at temperatures as
low as − 12 °C. This α/β protein is highly conserved and plays a key
role in iron homeostasis as an iron chaperone. In contrast to other
frataxin homologs, chemical and temperature unfolding experiments showed
that the thermodynamic stability of pFXN is strongly modulated by pHs:
ranging from 5.5 ± 0.9 (pH 6.0) to 0.9 ± 0.3 kcal mol− 1 (pH 8.0). This protein was crystallized and its X-ray structure solved at 1.45 Å. Comparison of B-factor profiles between Escherichia coli and P. ingrahamii
frataxin variants (51% of identity) suggests that, although both
proteins share the same structural features, their flexibility
distribution is different. Molecular dynamics simulations showed that
protonation of His44 or His67 in pFXN lowers the mobility of regions
encompassing residues 2030 and the C-terminal end, probably through
favorable electrostatic interactions with residues Asp27, Glu42 and
Glu99. Since the C-terminal end of the protein is critical for the
stabilization of the frataxin fold, the predictions presented may be
reporting on the microscopic origin of the decrease in global stability
produced near neutral pH in the psychrophilic variant. We propose that
suboptimal electrostatic interactions may have been an evolutionary
strategy for the adaptation of frataxin flexibility and function to cold
environments.