Substitution rates in α-helical transmembrane proteins

Timothy J. Stevens*, Isaiah T. Arkin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

It has been shown previously that some membrane proteins have a conserved core of amino acid residues. This idea not only serves to orient helices during model building exercises but may also provide insight into the structural role of residues mediating helix-helix interactions. Using experimentally determined high-resolution structures of α-helical transmembrane proteins we show that, of the residues within the hydrophobic transmembrane spans, the residues at lipid and subunit interfaces are more evolutionarily variable than those within the lipid-inaccessible core of a polypeptide's transmembrane domain. This supports the idea that helix-helix interactions within the same polypeptide chain and those at the interface between different polypeptide chains may arise in distinct ways. To show this, we use a new method to estimate the substitution rate of an amino acid residue given an alignment and phylogenetic tree of closely related proteins. This method gives better sensitivity in the otherwise-conserved transmembrane domains than a conventional similarity analysis and is relatively insensitive to the sequences used.

Original languageAmerican English
Pages (from-to)2507-2517
Number of pages11
JournalProtein Science
Volume10
Issue number12
DOIs
StatePublished - 2001

Keywords

  • Evolutionary conservation
  • Lipid bilayer
  • Phylogeny
  • Protein structure
  • Sequence alignment

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