Blog

Cover Article in JBC

JBC_coverOur image was selected as a cover article for the 21st December edition of JBC!

The image represents different orientations of the tetrahedral assembly of a wheat small heat shock protein (sHSP). These proteins form dimers, that in turn assemble in more complex architectures.

In our work we show that sHSP dimers (a single one highlighted in yellow in the image) are in equilibrium with the oligomeric form and act as the initial encounter species to capture denaturing substrates.

[image produced with VMD with Tachyon ray tracing, and composed with Gimp]

It takes a dimer to tango

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Under changes in conditions as diverse as temperature, oxidation or pH, proteins in an organism may undergo harmful denaturation. Small Heat Shock proteins act as “paramedics of the cell”: during such events they quicky intervene by binding nascently unfolding proteins, leading them to refolding or denaturation pathways. Small heat shock proteins are ubiquitous in all kingdoms of life, but especially effective in plants: after all, plants cannot escape from harsh environmental conditions!

Collaborating with Benesch (University of Oxford) and Vierling (UMass) groups, we have contributed to shedding light into the mode of action of small Heat Shock Proteins in wheat and pea.

We describe a mechanism whereby dimers of these proteins are responsible for capturing their substrate, before assemblying into larger complexes. With our own integrative modelling methods using distance restraints and collision cross-section measurements, we  demonstrate that small heat shock protein dimers assemble into characteristic tetrahedral structures (see on the right).

These results point towards ways to design small heat shock proteins customized to function at desired temperatures.

Santhanagopalan I., Degiacomi M.T., Shepherd D.A., Hochberg G.K.A., Justin L.P. Benesch J.L.P.,  Vierling E., (2018). It takes a dimer to tango: Oligomeric small heat shock proteins dissociate to capture substrate, Journal of Biological Chemisty

Mutation, where are you?

Our homology model of TBC1D24 is featured in a journal article on Human Molecular Genetics. Mutations in this protein are responsible for a broad range of diseases, including epilepsy, DOORS syndrome and hearing loss.

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Our model complements the titanic experimental effort of Dr. Mattéa Finelli and collaborators, unveiling that TBC1D24 is crucial for normal presynaptic function, and that disease-causing mutations affect neuronal development and survival.

M. Finelli et al, The epilepsy-associated protein TBC1D24 is required for normal development, survival and vesicle trafficking in mammalian neuron, Human Molecular Genetics, 2018

Venkat joins the group!

Welcome to Dr. Venkata Krishnan Ramaswamy, the first PDRA of our group! Venkat has a background in pharmacoinformatics, and molecular modelling, acquired during his graduate studies in NIPER (S.A.S. Nagar, India) and PhD University of Cagliary (Italy). In our group, Venkat will develop and apply methods combining molecular dynamics simulations and deep learning to characterize protein conformational space.

Welcome to Samuel!

Welcome to Samuel Musson, who joins us this academic year for his Masters project. Samuel, a Durham University student in Chemistry, will focus on the characterization of peptide-lipid interactions.

Postdoctoral position available

A 2-year PDRA position is available in our group, working on the EPSRC-funded project Software for Experimentally Driven Macromolecular Modelling.

The work will involve development and application of novel integrative modelling methodologies for the study of flexible protein monomers and the prediction of their multimeric arrangement. The position is available from October 2018.  Full information and application form on Durham University vacancies site (job ID: 015726). Contact Matteo matteo.t.degiacomi@durham.ac.uk for informal inquries.

Physics of Life Summer School

This week, Durham University is hosting the Physics of Life Network’s summer schoolNew approaches to biomolecular structure, dynamics and function“. This is an exciting learning and exchange opportunity for researchers having different backgrounds, but a common interest in the life sciences.

Lucas is presenting a poster on his work, aimed at developing novel volumetric representations accurately recapitulating protein intrinsic dynamics.