Cetacean Toll-like receptor 4 and myeloid differentiation factor 2, and possible cetacean-specific responses against Gram-negative bacteria.
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.
Shishido
Reiko
R
Japan Agency for Marine-Earth Science and Technology, Yokosuka, Kanagawa 247-0061, Japan.
Ohishi
Kazue
K
Suzuki
Rintaro
R
Takishita
Kiyotaka
K
Ohtsu
Dai
D
Okutsu
Kenji
K
Tokutake
Koji
K
Katsumata
Etsuko
E
Bando
Takeharu
T
Fujise
Yoshihiro
Y
Murayama
Tsukasa
T
Maruyama
Tadashi
T
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*
D048868:Adaptor Proteins, Signal Transducing; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4