title: Relation between sequence and structure in membrane proteins.
abstract: BACKGROUND
  Integral polytopic membrane proteins contain only two types of folds in their transmembrane domains: α-helix bundles and β-barrels. The increasing number of available crystal structures of these proteins permits an initial estimation of how sequence variability affects the structure conservation in their transmembrane domains. We, thus, aim to determine the pairwise sequence identity necessary to maintain the transmembrane molecular architectures compatible with the hydrophobic nature of the lipid bilayer.
  
  
  RESULTS
  Root-mean-square deviation (rmsd) and sequence identity were calculated from the structural alignments of pairs of homologous polytopic membrane proteins sharing the same fold. Analysis of these data reveals that transmembrane segment pairs with sequence identity in the so-called 'twilight zone' (20-35%) display high-structural similarity (rmsd < 1.5 Å). Moreover, a large group of β-barrel pairs with low-sequence identity (<20%) still maintain a close structural similarity (rmsd < 2.5 Å). Thus, we conclude that fold preservation in transmembrane regions requires less sequence conservation than for globular proteins. These findings have direct implications in homology modeling of evolutionary-related membrane proteins.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Grup de Recerca en Bioinformàtica i Estadística Mèdica, Departament de Biologia de Sistemes, Escola Politècnica Superior, Universitat de Vic, 08500 Vic, Barcelona, Catalonia, Spain. Mireia.Olivella@uvic.cat
authors.forename: Mireia
authors.initials: M
authors.lastname: Olivella
authors.forename: Angel
authors.initials: A
authors.lastname: Gonzalez
authors.forename: Leonardo
authors.initials: L
authors.lastname: Pardo
authors.forename: Xavier
authors.initials: X
authors.lastname: Deupi
mesh_terms: D000595:Amino Acid Sequence; D017124:Conserved Sequence; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein
chemical_list: D008565:Membrane Proteins