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Bishnoi R , Sousa GL , Contet A , Day CJ , Hou CD , Profitt LA , Singla D , Jennings MP , Valentine AM , Povelones M , Baxter RHG
Solution structure, glycan specificity and of phenol oxidase inhibitory activity of Anopheles C-type lectins CTL4 and CTLMA2
Sci Rep. 2019 Oct 23;9(1) :15191
PMID: 31645596    PMCID: PMC6811590    URL: https://www.ncbi.nlm.nih.gov/pubmed/31645596
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Abstract
Malaria, the world's most devastating parasitic disease, is transmitted between humans by mosquitoes of the Anopheles genus. An. gambiae is the principal malaria vector in Sub-Saharan Africa. The C-type lectins CTL4 and CTLMA2 cooperatively influence Plasmodium infection in the malaria vector Anopheles. Here we report the purification and biochemical characterization of CTL4 and CTLMA2 from An. gambiae and An. albimanus. CTL4 and CTLMA2 are known to form a disulfide-bridged heterodimer via an N-terminal tri-cysteine CXCXC motif. We demonstrate in vitro that CTL4 and CTLMA2 intermolecular disulfide formation is promiscuous within this motif. Furthermore, CTL4 and CTLMA2 form higher oligomeric states at physiological pH. Both lectins bind specific sugars, including glycosaminoglycan motifs with beta1-3/beta1-4 linkages between glucose, galactose and their respective hexosamines. Small-angle x-ray scattering data supports a compact heterodimer between the CTL domains. Recombinant CTL4/CTLMA2 is found to function in vivo, reversing the enhancement of phenol oxidase activity in dsCTL4-treated mosquitoes. We propose these molecular features underline a common function for CTL4/CTLMA2 in mosquitoes, with species and strain-specific variation in degrees of activity in response to Plasmodium infection.
Notes
2045-2322 Bishnoi, Ritika Sousa, Gregory L Contet, Alicia Day, Christopher J Hou, Chun-Feng David Profitt, Lauren A Singla, Deepak Jennings, Michael P Valentine, Ann M Povelones, Michael Baxter, Richard H G Journal Article England Sci Rep. 2019 Oct 23;9(1):15191. doi: 10.1038/s41598-019-51353-z.