4HS5

Frataxin from Psychromonas ingrahamii as a model to study stability modulation within CyaY protein family

Summary for 4HS5

• Entry DOI: 10.2210/pdb4hs5/pdb
• Descriptor: Protein CyaY (2 entities in total)
• Functional Keywords: pfxn, frataxin, cyay, psychromonas ingrahamii, frataxin-like domain, cyay protein family (pfam id pf01491), iron homeostasis-redox balance, metal binding protein
• Biological source: Psychromonas ingrahamii
• Total number of polymer chains: 2
• Total formula weight: 24590.77

Authors

Roman, E.A.,Cousido-siah, A.,Mitschler, A.,Podjarny, A.,Santos, J. (deposition date: 2012-10-29, release date: 2013-03-13, Last modification date: 2023-11-08)

Primary citation

Roman, E.A.,Faraj, S.E.,Cousido-Siah, A.,Mitschler, A.,Podjarny, A.,Santos, J.
Frataxin from Psychromonas ingrahamii as a model to study stability modulation within the CyaY protein family
Biochim.Biophys.Acta, 1834:1168-1180, 2013

PubMed Abstract: 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 (pH6.0) to 0.9±0.3kcalmol(-1) (pH8.0). This protein was crystallized and its X-ray structure solved at 1.45Å. 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 20-30 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.

PubMed: 23429177
DOI: 10.1016/j.bbapap.2013.02.015

Experimental method

X-RAY DIFFRACTION (1.45 Å)