Modeling membrane protein structures
Part 3. Proteomics
3.7. Structural Proteomics
Short Specialist Review
Published Online: 15 OCT 2004
Copyright © 2005 John Wiley & Sons, Ltd
Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics
How to Cite
Arinaminpathy, Y. and Sansom, M. S. 2004. Modeling membrane protein structures. Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics. 3:3.7:103.
- Published Online: 15 OCT 2004
Integral membrane proteins play a central role in many biological activities of cells. Only a small number of structures are known at high resolution, in contrast to the relatively large fraction (∼25%) of genes encoding membrane proteins. It is somewhat easier to model the structure of a transmembrane protein than that of a globular protein as a consequence of the constraints imposed by the transmembrane environment. Modeling of membrane proteins plays an important role as the majority of experimentally determined structures are bacterial homologs of human proteins. The first stage of membrane protein modeling is to predict the location and extent of the transmembrane α-helices. A number of sequence-based methods are available for this, and the consensus accuracy of prediction is ∼80%. If a three-dimensional structure is available for a homolog of the target membrane protein, this structure may be used as a template for homology modeling of the target protein. Secondary structure prediction and experimentally derived restraints may be used to aid the process of homology modeling. Once generated, a model may be evaluated in terms of general principles of membrane protein structure, such as the presence of bands of tryptophan and tyrosine side chains on the membrane protein surface positioned so as to interact with lipid bilayer headgroups. The stability and dynamic behavior of the membrane protein model may be investigated via molecular dynamics simulations. As an example of the overall process, generation of a model of the transmembrane domain of a prokaryotic glutamate receptor (GluR0) using a bacterial potassium channel (KcsA) as a template is described.
- membrane proteins;
- homology modeling;
- transmembrane helices;
- structural bioinformatics;
- structure prediction