A novel small heat shock protein 12.6 (HSP12.6) from Brugia malayi functions as a human IL-10 receptor binding protein.
Phage display cDNA expression library of the third stage larvae (L3) of Brugia malayi was screened for identifying target(s) that bound to the human interleukin-10 receptor (huIL10R). This iterative screening identified an insert that showed significant homology to Caenorhabditis elegans HSP12.6. The gene was designated B. malayi HSP12.6 (BmHSP12.6) and has orthologues in several gastrointestinal nematode genome (Ancylostoma caninum, Ascaris lumbricoides and Ascaris suum) but the gene or gene product has not been studied further in these parasites. Structural analyses of BmHSP12.6 showed that it has a highly conserved alpha-crystallin central domain that is characteristic of other small heat shock proteins (HSPs). BmHSP12.6 has a short N-terminal domain and an unusually small C-terminal domain flanking the crystallin domain suggesting that this protein belongs to a novel class of small HSPs. BmHSP12.6 appears to be differentially transcribed with highest expression in the vertebrate stages of the parasite (L4, adult and mf) compared to its mosquito vector stage (L3). More importantly recombinant BmHSP12.6 bound to huIL10R in a dose dependent fashion and inhibited the binding of human IL-10 (huIL10) to huIL10R in vitro. rBmHSP12.6 also enhanced the growth and proliferation of MC/9 mast cells in vitro similar to huIL10. This study thus describes a novel small HSP from B. malayi that has the capacity to bind to huIL10R, block binding of huIL10 to huIL10R and function similar to huIL10.
Gnanasekar
Munirathinam
M
Department of Biomedical Sciences, University of Illinois, College of Medicine, Rockford, IL 61107, USA.
Anandharaman
Veerapathran
V
Anand
Setty Balakrishnan
SB
Nutman
Thomas B
TB
Ramaswamy
Kalyanasundaram
K
D000595:Amino Acid Sequence; D000818:Animals; D017178:Brugia malayi / Q000276:immunology*; D017173:Caenorhabditis elegans / Q000235:genetics; D049109:Cell Proliferation; D018509:DNA, Helminth / Q000737:chemistry / Q000235:genetics; D020869:Gene Expression Profiling; D050888:Heat-Shock Proteins, Small / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015801:Helminth Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D008407:Mast Cells / Q000276:immunology; D008969:Molecular Sequence Data; D019151:Peptide Library; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D053701:Receptors, Interleukin-10 / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
D018509:DNA, Helminth; D050888:Heat-Shock Proteins, Small; D015801:Helminth Proteins; D019151:Peptide Library; D053701:Receptors, Interleukin-10