Three isoforms of complement properdin factor P in trout: cloning, expression, gene organization and constrained modeling.
Properdin is a plasma glycoprotein and the only known naturally occurring positive regulator of the complement system, stabilizing the alternative pathway convertase (C3bBb). In order to elucidate the molecular evolution of properdin factor P (pfc), here we report the cloning and characterization of three gene isoforms of properdin in rainbow trout (Oncorhynchus mykiss). The predicted polypeptide sequences of trout properdins pfc1, pfc2 and pfc3 (447, 449 and 447 amino acids, respectively) share 78-90% identity to each other, showing the highest identity score (47%) with their zebrafish ortholog protein. The overall identity with human, mouse and xenopus properdin polypeptides is 44%, 42% and 45%, respectively. The 'domain' architecture of trout properdins resembles that of the mammalian counterpart proteins, composed of six thrombospondin repeat type 1 domains (TSR-1-TSR-6). TSR domains of the three trout properdin isoforms seem to adopt the folding pattern of human thrombospondin 1 TSP-1 domains, where each TSP-1 domain forms an antiparallel three-stranded structure that consists of alternative stacked layers of Trp and Arg residues from respective strands capped by disulfide bonds on each end. The trout pfc2 and pfc3 genes are arranged in nine and ten exons, respectively, which span approximately 3.5kb of the genome. In contrast to the expression profile of the properdin gene in mammals, liver is the main source of the trout properdin mRNA transcripts. In a phylogenetic analysis, trout pfc1, pfc2 and pfc3 genes are clustered with their orthologs from other teleost species. This is the first report of three separate genes coding for properdin factor P in a vertebrate species.
Chondrou
Maria
M
Department of Biology, School of Medicine, University of Patras, 26 500 Patras, Greece.
Papanastasiou
Anastasios D
AD
Spyroulias
Georgios A
GA
Zarkadis
Ioannis K
IK
D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D017686:Oncorhynchus mykiss / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D011414:Properdin / Q000096:biosynthesis / Q000235:genetics*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D020539:Sequence Analysis, Protein; D017386:Sequence Homology, Amino Acid
D020033:Protein Isoforms; D011414:Properdin