A Protein Chemistry Approach to the Modelling of Integral Membrane Proteins

Summary

The site of attachment of chemical probes and residues specifically modified by biological processes can be identified by protein sequencing. When such approaches are used with integral membrane proteins, the information is particularly valuable since it can help determine the disposition of the polypeptide chain in the bilayer, the number of transmembrane regions, the orientation of the individual helices within the bilayer and the approximate position of important functional sites. When combined with biophysical data on the relative position of these helices, some appreciation can be obtained of the 3-dimensional structure of the protein. This contribution illustrates the use of this strategy for the visual light receptor rhodopsin and the proton channel of the vacuolar H⁺-ATPase. The resultant models are assessed in terms of the functional properties of these proteins and their evolutionary homologues.