Abstract

During blood-feeding, mosquito saliva is injected into the skin to facilitate blood meal acquisition. D7 proteins are among the most abundant components of the mosquito saliva. Here we report the ligand binding specificity and physiological relevance of two D7 long proteins from Culex quinquefasciatus mosquito, the vector of filaria parasites or West Nile viruses. CxD7L2 binds biogenic amines and eicosanoids. CxD7L1 exhibits high affinity for ADP and ATP, a binding capacity not reported in any D7. We solve the crystal structure of CxD7L1 in complex with ADP to 1.97 Å resolution. The binding pocket lies between the two protein domains, whereas all known D7s bind ligands either within the N- or the C-terminal domains. We demonstrate that these proteins inhibit hemostasis in ex vivo and in vivo experiments. Our results suggest that the ADP-binding function acquired by CxD7L1 evolved to enhance blood-feeding in mammals, where ADP plays a key role in platelet aggregation.

D7 proteins are highly abundant in the salivary glands of several blood feeding insects. Here, the authors study the ligand binding specificity and physiological roles of the mosquito D7 proteins CxD7L1 and CxD7L2, showing that CxD7L1 acquired ADP-binding properties to enhance blood feeding in mammals.

Details

Title
ADP binding by the Culex quinquefasciatus mosquito D7 salivary protein enhances blood feeding on mammals
Author
Martin-Martin, Ines 1   VIAFID ORCID Logo  ; Paige, Andrew 1   VIAFID ORCID Logo  ; Valenzuela Leon Paola Carolina 1   VIAFID ORCID Logo  ; Gittis, Apostolos G 1 ; Kern, Olivia 1 ; Bonilla, Brian 1 ; Chagas Andrezza Campos 1 ; Ganesan Sundar 1 ; Smith, Leticia Barion 1 ; Garboczi, David N 1 ; Calvo, Eric 1   VIAFID ORCID Logo 

 National Institutes of Health, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Rockville, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2411085680
Copyright
© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020. 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.