title: Conserved conformational dynamics of membrane fusion protein transmembrane domains and flanking regions indicated by sequence statistics.
abstract: SNARE proteins and fusogenic viral membrane proteins represent the major classes of integral membrane proteins that mediate fusion of eukaryotic lipid bilayers. Although both classes have different primary structures, they share a number of basic architectural features. There is ample evidence that the fusogenic function of representative fusion proteins is influenced by the primary structure of the single transmembrane domain (TMD) and the region linking it to the soluble assembly domains. Here, we used comprehensive non-redundant datasets to examine potential over- and underrepresentation of amino acid types in the TMDs and flanking regions relative to control proteins that share similar biosynthetic origins. Our results reveal conserved overall and/or site-specific enrichment of β-branched residues and Gly within the TMDs, underrepresentation of Gly and Pro in regions flanking the TMD N-terminus, and overrepresentation of the same residue types in C-terminal flanks of SNAREs and viral fusion proteins. Furthermore, the basic Lys and Arg are enriched within SNARE N-terminal flanking regions. These results suggest evolutionary conservation of key structural features of fusion proteins and are discussed in light of experimental findings that link these features to the fusogenic function of these proteins.
authors.affiliation: Department für biowissenschaftliche Grundlagen, Lehrstuhl für Genomorientierte Bioinformatik, Technische Universität München, Freising, Germany.
authors.forename: Sindy
authors.initials: S
authors.lastname: Neumann
authors.forename: Dieter
authors.initials: D
authors.lastname: Langosch
mesh_terms: D000595:Amino Acid Sequence; D050576:Membrane Fusion Proteins / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D050600:SNARE Proteins / Q000737:chemistry*; D014760:Viral Fusion Proteins / Q000737:chemistry
chemical_list: D050576:Membrane Fusion Proteins; D050600:SNARE Proteins; D014760:Viral Fusion Proteins