title: The 2.0-A crystal structure of tachylectin 5A provides evidence for the common origin of the innate immunity and the blood coagulation systems.
abstract: Because invertebrates lack an adaptive immune system, they had to evolve effective intrinsic defense strategies against a variety of microbial pathogens. This ancient form of host defense, the innate immunity, is present in all multicellular organisms including humans. The innate immune system of the Japanese horseshoe crab Tachypleus tridentatus, serving as a model organism, includes a hemolymph coagulation system, which participates both in defense against microbes and in hemostasis. Early work on the evolution of vertebrate fibrinogen suggested a common origin of the arthropod hemolymph coagulation and the vertebrate blood coagulation systems. However, this conjecture could not be verified by comparing the structures of coagulogen, the clotting protein of the horseshoe crab, and of mammalian fibrinogen. Here we report the crystal structure of tachylectin 5A (TL5A), a nonself-recognizing lectin from the hemolymph plasma of T. tridentatus. TL5A shares not only a common fold but also related functional sites with the gamma fragment of mammalian fibrinogen. Our observations provide the first structural evidence of a common ancestor for the innate immunity and the blood coagulation systems.
authors.affiliation: Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Am Klopferspitz 18a, 82152 Martinsried, Germany. kairies@biochem.mpg.de
authors.forename: N
authors.initials: N
authors.lastname: Kairies
authors.forename: H G
authors.initials: HG
authors.lastname: Beisel
authors.forename: P
authors.initials: P
authors.lastname: Fuentes-Prior
authors.forename: R
authors.initials: R
authors.lastname: Tsuda
authors.forename: T
authors.initials: T
authors.lastname: Muta
authors.forename: S
authors.initials: S
authors.lastname: Iwanaga
authors.forename: W
authors.initials: W
authors.lastname: Bode
authors.forename: R
authors.initials: R
authors.lastname: Huber
authors.forename: S
authors.initials: S
authors.lastname: Kawabata
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001777:Blood Coagulation; D001798:Blood Proteins / Q000737:chemistry* / Q000276:immunology / Q000502:physiology; D018360:Crystallography, X-Ray; D019143:Evolution, Molecular; D005340:Fibrinogen / Q000737:chemistry; D006737:Horseshoe Crabs; D006801:Humans; D007113:Immunity, Innate; D037102:Lectins / Q000737:chemistry* / Q000276:immunology / Q000502:physiology; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
chemical_list: D001798:Blood Proteins; D037102:Lectins; D008024:Ligands; C121518:TL-5A protein, Tachypleus tridentatus; D005340:Fibrinogen