Mackereth Lab IECB | Bordeaux | France

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WELCOME to the Mackereth
NMR group

Cameron Mackereth
The lab is focussed on the structural details of how proteins and nucleic acids come together to form complexes. We use a combination of biochemical methods to probe the way in which the pieces of these biomolecules are assembled, but our main technique is nuclear magnetic resonance (NMR) spectroscopy. 

NOESY Structure-4 Structure-3 Structure-2 Structure-1 Structure

Research Overview

There is increasing evidence in support of a model of cellular biochemistry in which most proteins exert their biological role through either transient or relatively stable multi-component macromolecular complexes. The key to understanding the function of these complexes lies in their structural investigation by a variety of biophysical methods. The lab studies molecular details of large protein-nucleic acid macromolecules using a variety of new NMR techniques as well as established biophysical approaches. For large complexes, we utilize a rigid body assembly of individually characterized structures using a combination of methods: domain orientation through the measurement of residual dipolar coupling (RDC) by NMR spectroscopy, overall shape determination by small angle neutron or X-ray scattering (SANS/SAXS), and incorporating molecular contact details from such techniques as NMR paramagnetic spin labelling to acquire information on long-range contacts, as well as in vitro mutational analysis and other binding assays. For smaller proteins and domains, standard NMR-based approaches are used, but with additional insight gained from RDC and spin label information. Equally important to the lab is the traditional strength of NMR as a tool to probe the dynamics of biological samples, the characterization of transient interactions, and the possibility to look at structures that exhibit a significant amount of unstructured elements.

Current projects include:

Proteins involved in RNA processing, especially alternative splicing.

Modification of histones. 

*************************************************  NEWS  ***********************************************

We welcome second year Masters student Amiirah Bibi Edoo and first year Masters student Daisy Awiti to our group!

Previous News Highlights

****************************************  RECENT PUBLICATIONS  **************************************

We are excited to present our work with two recent cover images:

Chemical biology: studying the interaction between a  synthetic quinoline-based foldamer and human carbonic anhydrase. In collaboration with the team of Ivan Huc, we have looked at the solution behaviour of a foldamer–protein complex by NMR and circular dichroism. Inspired by the atomic details of the previous crystal structure we looked specifically at foldamer-mediated protein dimerization and the process of foldamer handedness induction. Looking at this hybrid complex in solution gives us clues as to how to design future foldamers to specifically interact with proteins. More to follow soon!
Jewginski, M., Fischer, L., Colombo, C., Huc, I., Mackereth, C.D. 2016. Solution observation of dimerization and helix handedness induction in a human carbonic anhydrase-helical aromatic amide foldamer complex. ChemBioChem 17:727-736.

A new trick for oligoureas. We have added our expertise in solution NMR spectroscopy to work led by the team of Gilles Guichard. The goal was to help in the characteization of a series of oligoureas that with a small change in sequence can exist as either a hexamer bundle or an extended channel. The extra properties of pH-sensitivity and, for the hexamer, a central hydrophobic cavity suggest that these oligoureas will have many interesting future uses.
Collie, G.W., Pulka-Ziach, K., Lombardo, C.M., Fremaux, J., Rosu, F., Decossas, M., Mauran, L., Lambert, O., Gabelica, V., Mackereth, C.D., Guichard, G. 2015. Shaping quaternary assemblies of water-soluble non-peptide helical foldamers by sequence manipulation. Nat. Chem. 7:871-878.

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