title: Cetacean Toll-like receptor 4 and myeloid differentiation factor 2, and possible cetacean-specific responses against Gram-negative bacteria.
abstract: Toll-like receptor 4 (TLR4) and myeloid differentiation factor 2 (MD-2) are essential for recognizing the lipopolysaccharides (LPS) of Gram-negative bacteria. We determined the sequences of cDNAs encoding TLR4 and MD-2 from cetaceans and generated three-dimensional (3D) models for a better understanding of their modes of interaction and LPS recognition. The 3D reconstructions showed that cetacean TLR4 and MD-2 formed a horseshoe-like structure comprised of parallel β-strands and a β-cup structure consisting of two anti-parallel β-sheets, respectively. The (TLR4-MD-2)(2) duplex-heterodimer was shown to form a symmetrical structure. Comparison with the interfaces of the complexes in other mammals revealed that cetacean TLR4s have some amino acid residue substitutions involved in duplex-heterodimer formation and in species variation for LPS recognition. These substitutions in the changed amino acid residues may alter the interaction among TLR4, MD-2, and LPS and modify the TLR4/MD-2 immunological responses.
authors.affiliation: Japan Agency for Marine-Earth Science and Technology, Yokosuka, Kanagawa 247-0061, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Shishido
authors.forename: Kazue
authors.initials: K
authors.lastname: Ohishi
authors.forename: Rintaro
authors.initials: R
authors.lastname: Suzuki
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Takishita
authors.forename: Dai
authors.initials: D
authors.lastname: Ohtsu
authors.forename: Kenji
authors.initials: K
authors.lastname: Okutsu
authors.forename: Koji
authors.initials: K
authors.lastname: Tokutake
authors.forename: Etsuko
authors.initials: E
authors.lastname: Katsumata
authors.forename: Takeharu
authors.initials: T
authors.lastname: Bando
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujise
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Murayama
authors.forename: Tadashi
authors.initials: T
authors.lastname: Maruyama
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D004289:Dolphins / Q000276:immunology*; D006090:Gram-Negative Bacteria / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D013045:Species Specificity; D051197:Toll-Like Receptor 4 / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D050685:Whale, Killer / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4