NMR structures of polytopic integral membrane proteins

Abstract

Membrane proteins represent up to 30% of the proteins in all organisms, they are involved in many biological processes and are the molecular targets for around 50% of validated drugs. Despite this, membrane proteins represent less than 1% of all high-resolution protein structures due to various challenges associated with applying the main biophysical techniques used for protein structure determination. Recent years have seen an explosion in the number of high-resolution structures of membrane proteins determined by NMR spectroscopy, especially for those with multiple transmembrane-spanning segments. This is a review of the structures of polytopic integral membrane proteins determined by NMR spectroscopy up to the end of the year 2010, which includes both β-barrel and α-helical proteins from a number of different organisms and with a range in types of function. It also considers the challenges associated with performing structural studies by NMR spectroscopy on membrane proteins and how some of these have been overcome, along with its exciting potential for contributing new knowledge about the molecular mechanisms of membrane proteins, their roles in human disease, and for assisting drug design.

Keywords::

• Polytopic integral membrane proteins
• structures
• nuclear magnetic resonance spectroscopy
• NMR
• solution-state
• solid-state

Acknowledgements

The author thanks Peter Henderson and Steve Homans (University of Leeds) and Malcolm Levitt (University of Southampton) for their support.

Declaration of interest: This work was funded by grants from the EPSRC (EP/G035695/1) and EU (201924, EDICT).The author reports no conflicts of interest. The author alone is responsible for the content and writing of the paper.