Lucas and Matteo attended the 4th N8 Byophysical and Biochemical Symposium in Sheffield. Matteo gave an invited talk about the group’s work on integrative modelling, and Lucas presented a poster and a flash talk about his development of an accurate scoring function for protein docking.
Our 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]
Our work, proposing a plausible mechanism for the origin of prebiotic peptides, is featured in Nature Communications’ “Early Earth Collection”! This collection summarizes recent published work aimed at characterizing early earth conditions, and the crucial though still hardly understood transition from geo to biochemistry. See the editorial here!
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!
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
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.
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
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 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.
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 email@example.com for informal inquries.
This week, Durham University is hosting the Physics of Life Network’s summer school “New 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.
Our article has been just published on PNAS! In this work we study the effect of specific protein-lipid interactions with a palette of techniques featuring native mass spectrometry, molecular dynamics and channel recording experiments alongside our own structural bioinformatics analysis (on the left in the figure).
We found that within membrane proteins there exists a huge amount of variability on the amount of charged amino acids exposed with lipid heads, and identified proteins that may modulate their function via specific pH-modulated interactions with the neighbouring bilayer. This is exemplified by the protein OmpF, a channel that remained open for longer times in the presence POPG lipids under acidic conditions.
So, what about this “think positive about negative” title? This refers to the observation that probing protein-lipid samples with both positive and negative electrospray ionization (the latter not commonly used in the word of native mass spectrometry) can provide precious insights into specific protein-lipid interactions. This actually, half jokingly, almost became the title of the paper!
Reference (currently in online form): Liko, I., et al., (2018). Lipid binding attenuates channel closure of the outer membrane protein OmpF. PNAS