Solvent disorder and protein dynamical transition

Protein dynamical transition (PDT) indicates the sudden activation of protein fluctuations above a critical temperature, Td ~ 220-240 K. The phenomenon has attracted the attention of scientists along the years because the possible implications. First, it has been strongly related to the role of the solvent environment surrounding the protein, and namely its physical changes. It is not surprising that many concepts coined in the community of liquids were transposed to scratch insights on the problem. Secondly, this problem represented the door through which the community active in neutron scattering entered heavily in the discussion about protein dynamics and function. Yet today, numerous  interesting works focusing on the protein dynamical transition appear in top-notch magazines, see e.g. Weik and coworkers discussed the correlation among water translation and protein fluctuation across the PDT [here] while Hong and coworkers claim that the transition is an intrinsic feature of the dry protein energy landscape [here]. We are participating to the debate, as presented in the post dedicated to Lindemann criterion. To better understand the relationship among protein motion and solvent behaviour, we have recently developed a methodology that using data from particle based simulations, can fruitfully estimate the change in the water  hydrogen bond connectivity, in space, in time, and in temperature. We show the PDT correlates to the sudden increase in the configurational disorder of the water HB network enveloping the proteins. Our finding links, in the spirit of the Adam–Gibbs relationship, the diffusivity of protein atoms, as quantified by the hydrogen mean-square displacements, and the thermodynamic solvent configurational entropy. Enjoy the paper here, and a comment in the P. Ball's blog Water in Biology.

Water helps life in extreme environments?

A few months ago we published an explorative work focusing on the possible contribution of water molecules buried in the interior of proteins to their different thermal stabilities [see here for the paper]. The study-case was a pair of homologous GTPase domains from a mesophilic and a hyperthermophilic organism, respectively. Now, we extended our approach by considering a large set of homologous pairs. Let's list the main findings. Firstly, for some homologues internal water gives a meaningful contribution to the stability gap in favour of the thermophilic variant. This was probed at ambient condition. Secondly, when considering the behaviour at high temperature, we found that thermophilic proteins are more keen to maintain their internal cavities wet, and therefore benefiting by this wetting. We propose that internal hydration can be viewed as an alternative tuneable variable  for the engineering of proteins with enhanced stability. Enjoy the manuscript here.

Solvation of halophilic proteins

My collaborators at the Institut of Biologie Structurale in Grenoble (FR), D. Madern and E. Girard along with the PhD student R. Tallon, just published an interesting work in Frontier (Microbiology/Extreme Microbiology), see the manuscript here. They report a detailed comparison between the structures of two homologous proteins: the halophilic tetrameric malate from the bacterium Salinibacter ruber (Sr) and the non-halophilic malate from the bacterium Chloroflexus aurantiacus (Ca). The core of the discussion concerns the role of hydration on extreme adaptation and relates to the different surface compositions of the two proteins, and the potential different coupling with the solvent layer.

First, the structures are resolved at very high-resolution. Second, the protein from Ca is resolved with a huge number of hydration molecules surrounding the protein surface and hydrating some internal locations. The presence of this well defined hydration layer around the non-halophilic protein allows to individuate precise closed structures of water, à voir pentagons, surrounding some hydrophobic patches of the surface. On the contrary the x-ray structure of the halophilic protein from the Sr bacterium lacks a well defined hydration layer and no clusters of water were visualized. Therefore the authors concluded that the chemical composition of the surface of the halophilic protein, enriched in negatively charged amino-acids, makes unfavorable for water to create extended closed networks of hydrogen bonds.

Then, and this is more speculative, the authors discuss how the enrichment in  negatively charged amino-acids could play a role for i) solubility in high-salt concentration and ii) salt-in effects observed in halophilic proteins.
Stay tuned on the blog because we are currently investigating how the life of a protein at ambient condition influences the stability of the water hydrogen bonds networks at the protein surface. For the moments, some hints from our past studies: i) role of protein surface on dynamics and structure of interfacial water (see here), ii) water networks at protein surface and protein stability (see here), iii) a molecular vision of protein hydration (see here), iv) proteins compositions and water dynamics (see here).

Halophile bacteria in Lake Natron, Tanzania