Research group leaders
Daniel Nietlispach
Membrane proteins represent approximately 35% of all the proteins in the genome but their native membrane environment makes them difficult targets to study. Despite their large abundance they are structurally underrepresented and account for less than 0.5% of the solved 3D structures. Over recent years NMR spectroscopy has developed into a powerful technique to study the structure and function of such proteins. One of the distinct advantages of using NMR spectroscopy over other structure determination techniques is its flexibility: the method can report on molecular structure, ligand binding, conformational changes and dynamical processes that can take place on a wide range of timescales.
Our group is interested in the study of 7-helical membrane proteins such as microbial rhodopsin and the large family of eukaryotic G protein-coupled receptors (GPCRs). Hundreds of GPCRs are involved in signal transduction across the plasma membrane, where they regulate a wide range of physiological processes. As only limited structural information is available, it is still unclear how these proteins work. NMR spectroscopy is one of our main tools to study such systems. The substantial size of these proteins requires some method development and recently we have pioneered the structure determination of a microbial seven-helical protein by NMR.
Lab members:
Mark Bostock, Leo Cheung, Duncan Crick, Antoine Gautier, Leena Makani, Rowina Westermeier, Yvonne Yu
Key publications:
1. Gautier, A., Kirkpatrick, J.P. and Nietlispach, D. (2008) Solution-state NMR spectroscopy of a seven-helix transmembrane protein receptor: Backbone assignment, secondary structure, and dynamics. Angew. Chem.-Int. Edit. 47, 7297-7300.
2. Gautier, A., Mott, H.R., Bostock, M.J., Kirkpatrick, J.P. and Nietlispach, D. (2010) Structure determination of the seven-helix transmembrane receptor sensory rhodopsin II by solution NMR spectroscopy. Nat. Struct. Mol. Biol. 17, 768-774.
3. Holland, D.J., Bostock, M.J., Gladden, L.F. and Nietlispach, D. (2011) Fast Multidimensional NMR Spectroscopy Using Compressed Sensing. Angew. Chem.-Int. Edit. 50, 6548-6551.