Understanding how membrane proteins fold using dipolar spectroscopy

Maxie M Roessler (primary)
School of Biological and Chemical Sciences
Queen Mary, University of London
Paula Booth (secondary)
Chemistry
King's College London

Abstract

Membrane proteins are essential building blocks in processes such as respiration and photosynthesis, and they are also the target of over half of all modern medicinal drugs. Their four-dimensional structure is known to be essential for function, yet our knowledge of how large and complex membrane proteins fold is in its infancy. Double electron-electron resonance (DEER) spectroscopy provides a new approach to tackle this challenge. In this project we will use site-directed spin labelling combined with DEER to unravel how members of the major facilitator superfamily of transporters fold and to begin to understand how respiratory complex I is assembled.


References

  1. Findlay, Rutherford, Henderson & Booth, 2010, The unfolding free energy of a two-domain transmembrane sugar transport protein, Proc Natl Acad Sci USA, 107, 18451-18456, DOI: 10.1073/pnas.1005729107
  2. Mchourab, Steed, Kazmier, 2011, Toward the fourth dimension of membrane protein structure: insight into dynamics from spin-labeling EPR spectroscopy, Structure, 19, 1549-1561, DOI: 10.1016/j.str.2011.10.009
  3. Jeschke, 2012, DEER distance measurements on proteins, Annu Rev Phys Chem, 63, 419-446, DOI: 10.1146/annurev-physchem-032511-143716
  4. Harris, N.J., Findlay, H.E., Simms, J., Liu, X., Booth, 2014, Relative domain folding and stability of a membrane transport protein, J Mol Biol, 426, 1812-1825, DOI: 10.1016/j.jmb.2014.01.012
  5. Roessler, King, Robinson, Armstrong, Harmer, Hirst, 2010, Direct assignment of EPR spectra to structurally defined iron-sulfur clusters in complex I by double electron–electron resonance, Proc Natl Acad Sci USA, 107, 1930-1935, DOI: 10.1073/pnas.0908050107

BBSRC Area
Molecules, cells and industrial biotechnology
Area of Biology
Chemical BiologyStructural Biology
Techniques & Approaches
BiochemistryBiophysicsChemistryMolecular BiologySimulation / Modelling