Kristoffer Illergard and Anni Kauko contributed equally to this work.
Why are polar residues within the membrane core evolutionary conserved?
Article first published online: 11 OCT 2010
Copyright © 2010 Wiley-Liss, Inc.
Proteins: Structure, Function, and Bioinformatics
Volume 79, Issue 1, pages 79–91, January 2011
How to Cite
Illergård, K., Kauko, A. and Elofsson, A. (2011), Why are polar residues within the membrane core evolutionary conserved?. Proteins, 79: 79–91. doi: 10.1002/prot.22859
- Issue published online: 30 NOV 2010
- Article first published online: 11 OCT 2010
- Accepted manuscript online: 23 AUG 2010 10:31AM EST
- Manuscript Accepted: 13 AUG 2010
- Manuscript Revised: 23 JUL 2010
- Manuscript Received: 7 APR 2010
- Swedish Research Councils, the Foundation for strategic research (SSF) and the EU 6'the Framework program through the EM-BRACE project. Grant Number: LSHG-CT-2004-512092
- Academy of Finland
- membrane proteins;
- polar residues;
- functional residues
Here, we present a study of polar residues within the membrane core of alpha-helical membrane proteins. As expected, polar residues are less frequent in the membrane than expected. Further, most of these residues are buried within the interior of the protein and are only rarely exposed to lipids. However, the polar groups often border internal water filled cavities, even if the rest of the sidechain is buried. A survey of their functional roles in known structures showed that the polar residues are often directly involved in binding of small compounds, especially in channels and transporters, but other functions including proton transfer, catalysis, and selectivity have also been attributed to these proteins. Among the polar residues histidines often interact with prosthetic groups in photosynthetic- and oxidoreductase-related proteins, whereas prolines often are required for conformational changes of the proteins. Indeed, the polar residues in the membrane core are more conserved than other residues in the core, as well as more conserved than polar residues outside the membrane. The reason is twofold; they are often (i) buried in the interior of the protein and (ii) directly involved in the function of the proteins. Finally, a method to identify which polar residues are present within the membrane core directly from protein sequences was developed. Applying the method to the set of all human membrane proteins the prediction indicates that polar residues were most frequent among active transporter proteins and GPCRs, whereas infrequent in families with few transmembrane regions, such as non-GPCR receptors. Proteins 2010. © 2010 Wiley-Liss, Inc.