Mackereth Lab IECB | Bordeaux | France

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WELCOME to the Mackereth
NMR group

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. 


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:

Nucleic acid recognition by proteins
Proteins involved in RNA processing, especially alternative splicing
Synthetic foldamer recognition of biomolecules

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

A very big welcome to Sébastien Campagne who joins us as a permanent researcher (CRCN) within the French National Institute of Health and Medical Research (Inserm).

We also welcome M2 student Agathe Ecoutin who will part of the ANR project 'AFFLIGEM'

New logo and new website. Our group is part of the Inserm unit U1212 (CNRS UMR 5320, Univ. Bordeaux) focused on the natural and artificial regulation of nucleic acids, or 'Acides nucléiques : Régulations Naturelle et Artificielle' (ARNA). We are happy to report that our unit has a new logo, and also that we are in the process of completing a new website.

Previous News Highlights

Current and past lab members

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

We are excited to present some of our recent work:

An unusal way to bind RNA. Recent work from a collaboration with former postoc Santosh Kumar Upadhyay revealed an uncommon mechanism of RNA-binding by the RNA-Recognition Module (RRM) domain of a protein factor involved in heart development. This splicing factor, RBM20, uses the RRM domain to interact with a UCUU RNA sequence in target mRNA that is important for a healthy heart, including the mRNA the codes for the titin protein. Mutations in the RBM20 protein can lead to disease such as dilated cardiomyopathy (DCM). By using biophysical techniques that include NMR spectroscopy, we have found that the RRM domain from RBM20 uses a coupled binding-folding mechanism for selective recognition of the UCUU sequence - in particular for selectivity towards the last uracil in the RNA motif. What we found is that an additional helix (helix a3) only forms when the final uracil is present in the RNA motif, and we also found that the presence of the final helix is required for high-affinity binding.
Upadhyay, S.K., Mackereth, C.D. 2020. Structural basis of UCUU RNA motif recognition by splicing factor RBM20.  Nucleic Acids Res. 48:4538-4550.

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