Elastic incoherent neutron scattering at ILL challenge the Lindemann criterion in proteins

November 29, 2017, Institut Laue-Langevin
An image of the Lysozyme protein while it undergoes melting

Proteins are the nano-machines that Nature uses to perform most of the processes critical for the metabolism in cells. One of the key goals of life and physical sciences revolves around understanding the structural and dynamic properties of the native, transition, intermediate, and denatured states of proteins. The denaturation transition – defined as the transition of proteins from their specific native functional state to the unfolded inoperative state – is of particular interest, as it is defining the boundaries of stability and functionality of the phase diagram of proteins.

Internal subnanosecond timescale motions are also key for – without these proteins could not even fold in their native structure. Furthermore, they are extremely sensitive to the amount and nature of the solvent surrounding the i.e. both the amplitude and rate of these dynamics can be greatly reduced when proteins are embedded in sugar-glass matrices.

Although science knows that these fast fluctuations guide protein conformational changes, their role for protein stability and unfolding still remains elusive.

The results of a novel study conducted at the Institut Laue-Langevin (ILL), through a collaboration between the CNRS' Laboratoire de Biochimie Théorique (France), the Universities of Perugia, Pisa and Verona (Italy) and the CNR (Italy), gave a renewed picture of the Lindemann criterion. When conducting elastic neutron scattering experiments, researchers found a common scaling toward a constant value for the local fluctuations of a model protein in different environments, when approaching the unfolding temperature.

Using the state-of-the-art instruments at ILL, namely the wide-Q range backscattering spectrometer IN13, the researchers conducted elastic incoherent neutron scattering experiments on the lysozyme protein, chicken egg-white lysozyme (CEWL) in the presence of different perdeurated matrices (D20, glycerol, and glucose). This allowed them to study the model protein's sub-nanosecond timescale dynamics in correspondence with the unfolding transition.

This experimental technique is highly sensitive to the motions of hydrogen atoms, and suitable for exploring protein motions on a pico to nano timescale. It yields precise quantitative measurements of the amplitude of protein internal motions in terms of the hydrogen mean-square displacements (MSD).

By combining elastic incoherent neutron scattering and advanced molecular dynamics simulations, they showed that, although different solvents modify the protein melting temperature, a unique dynamical regime is attained when close to thermal unfolding in all solvents tested.

This is reminiscent of the famous Lindemann criterion introduced in 1910, where F.A. Lindemann developed a practical criterion to predict the melting temperature of crystals. Furthermore, the analogy between melting of inorganic crystals and native biomolecules suggests that these seemingly very different systems may share behaviour in corresponding phase transitions.

The common scaling for the protein MSD at melting point not only sheds light on the relationship between protein flexibility and stability, but also opens the possibility to predict protein unfolding in special environments (e.g. the cell interior) by following thermal, local fluctuations.

The criterion they propose can also be applied to investigate the temperature range where micro-organisms thrive e.g. at extreme temperature and pressure conditions in the deep sea or even in space.

This research potentially lays the foundation for a deeper understanding of the folding and unfolding of proteins, which are crucial processes in the metabolism of cells, regulation of biological activity and targeting of proteins to different cellular locations.

Additionally, understanding the functions of dynamic is key for biotechnology and pharmaceutical industries, where therapeutic principles based on proteins are worth approximately $30 billion in the US market alone.

Explore further: How water molecules dance to activate proteins

More information: Marina Katava et al. Critical structural fluctuations of proteins upon thermal unfolding challenge the Lindemann criterion, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1707357114

Related Stories

How water molecules dance to activate proteins

March 17, 2015

An international team of researchers has shed light on the molecular mechanism behind the importance of water for functional protein dynamics. The scientists have discovered that water's ability to flow on the surface of ...

Investigating folding stability and dynamics of proteins

July 5, 2017

Hydrogels are polymer materials that can absorb a large amount of water, making them flexible like human tissue. They are used in a number of medical applications, including contact lenses, wound dressings, and facial reconstruction.

Catching a glimpse at enzymes on the job

January 31, 2017

AAA+ ATPases are a large family of ubiquitous enzymes with multiple tasks, including the remodelling of the cellular proteome, i.e. the ensemble of proteins in a biological cell. A subfamily, so-called unfoldases, recognize, ...

A tale of two roads into protein unfolding

May 11, 2015

You are taking a class on origami and Mr. Otaki asks you to fold that little red piece of paper into a very elaborate design. You have to do it in a very short time. You try your best but you fail. Your origami sucks!

Recommended for you

Chemists characterize the fatal fungus among us

July 19, 2018

Life-threatening fungal infections affect more than two million people worldwide. Effective antifungal medications are very limited. Until now, one of the major challenges is that the fungal cell wall is poorly understood, ...

Infrared sensor as new method for drug discovery

July 19, 2018

Using an infrared sensor, biophysicists at Ruhr-Universität Bochum (RUB) have succeeded in analysing quickly and easily which active agents affect the structure of proteins and how long that effect lasts. Thus, Prof Dr. ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.