title: A novel human tectonin protein with multivalent beta-propeller folds interacts with ficolin and binds bacterial LPS.
abstract: BACKGROUND
  Although the human genome database has been completed a decade ago, approximately 50% of the proteome remains hypothetical as their functions are unknown. The elucidation of the functions of these hypothetical proteins can lead to additional protein pathways and revelation of new cascades. However, many of these inferences are limited to proteins with substantial sequence similarity. Of particular interest here is the Tectonin domain-containing family of proteins.
  
  
  RESULTS
  We have identified hTectonin, a hypothetical protein in the human genome database, as a distant ortholog of the limulus galactose binding protein (GBP). Phylogenetic analysis revealed strong evolutionary conservation of hTectonin homologues from parasite to human. By computational analysis, we showed that both the hTectonin and GBP form beta-propeller structures with multiple Tectonin domains, each containing beta-sheets of 4 strands per beta-sheet. hTectonin is present in the human leukocyte cDNA library and immune-related cell lines. It interacts with M-ficolin, a known human complement protein whose ancient homolog, carcinolectin (CL5), is the functional protein partner of GBP during infection. Yeast 2-hybrid assay showed that only the Tectonin domains of hTectonin recognize the fibrinogen-like domain of the M-ficolin. Surface plasmon resonance analysis showed real-time interaction between the Tectonin domains 6 & 11 and bacterial LPS, indicating that despite forming 2 beta-propellers with its different Tectonin domains, the hTectonin molecule could precisely employ domains 6 & 11 to recognise bacteria.
  
  
  CONCLUSIONS
  By virtue of a recent finding of another Tectonin protein, leukolectin, in the human leukocyte, and our structure-function analysis of the hypothetical hTectonin, we propose that Tectonin domains of proteins could play a vital role in innate immune defense, and that this function has been conserved over several hundred million years, from invertebrates to vertebrates. Furthermore, the approach we have used could be employed in unraveling the characteristics and functions of other hypothetical proteins in the human proteome.
authors.affiliation: Computational and Systems Biology, Singapore-MIT Alliance, Singapore, Singapore.
authors.forename: Diana Hooi Ping
authors.initials: DH
authors.lastname: Low
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Ang
authors.forename: Quan
authors.initials: Q
authors.lastname: Yuan
authors.forename: Vladimir
authors.initials: V
authors.lastname: Frecer
authors.forename: Bow
authors.initials: B
authors.lastname: Ho
authors.forename: Jianzhu
authors.initials: J
authors.lastname: Chen
authors.forename: Jeak Ling
authors.initials: JL
authors.lastname: Ding
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018076:DNA, Complementary; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D020349:Surface Plasmon Resonance; D000097604:Ficolins
chemical_list: D018076:DNA, Complementary; D037102:Lectins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D000097604:Ficolins; C111170:tectonin I