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 β1-3/β1-4 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.

Details

Title
Solution structure, glycan specificity and of phenol oxidase inhibitory activity of Anopheles C-type lectins CTL4 and CTLMA2
Author
Bishnoi, Ritika 1 ; Sousa, Gregory L 2 ; Contet, Alicia 3 ; Day, Christopher J 4 ; Chun-Feng, David Hou 1 ; Profitt, Lauren A 5 ; Singla, Deepak 6 ; Jennings, Michael P 4 ; Valentine, Ann M 5 ; Povelones, Michael 2 ; Baxter, Richard H G 7 

 Department of Medical Genetics & Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA 
 School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA 
 Department of Chemistry, Yale University, New Haven, Connecticut, USA; Centre d’Immunologie Pierre Fabre, Julien-en-Genevois, France 
 Institute of Glycomics, Griffith University, Queensland, Australia 
 Department of Chemistry, Temple University, Philadelphia, PA, USA 
 Laboratory of Host-Parasite Interaction Studies, National Institute of Malaria Research, Dwarka, India; School of Agricultural Biotechnology, Punjab Agricultural University, Ludhiana, Punjab, India 
 Department of Medical Genetics & Molecular Biochemistry, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA; Department of Chemistry, Yale University, New Haven, Connecticut, USA 
Pages
1-14
Publication year
2019
Publication date
Oct 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2309515051
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.