Structure of Aedes aegypti procarboxypeptidase B1 and its binding with Dengue virus for controlling infection
| Autor: | Donald Heng Rong Ting, Alonso Sylvie, Digant Nayak, Yu-Keung Mok, Fakhriedzwan Idris, Yeu Khai Choong, Edem Gavor, Nikhil Kumar Tulsian, Hariharan Sivaraman, R. Manjunatha Kini, J. Sivaraman |
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| Rok vydání: | 2021 |
| Předmět: |
Ecology
biology Health Toxicology and Mutagenesis Protein domain Midgut Plant Science Aedes aegypti Dengue virus medicine.disease_cause biology.organism_classification Biochemistry Genetics and Molecular Biology (miscellaneous) Carboxypeptidase Virology Mosquito control biology.protein medicine Parasite hosting Pathogen |
| Zdroj: | Life Science Alliance. 5:e202101211 |
| ISSN: | 2575-1077 |
| Popis: | Metallocarboxypeptidases play critical roles in the development of mosquitoes and influence pathogen/parasite infection of the mosquito midgut. Here, we report the crystal structure of Aedes aegypti procarboxypeptidase B1 (PCPBAe1), characterized its substrate specificity and mechanism of binding to and inhibiting Dengue virus (DENV). We show that the activated PCPBAe1 (CPBAe1) hydrolyzes both Arg- and Lys-substrates, which is modulated by residues Asp251 and Ser239. Notably, these residues are conserved in CPBs across mosquito species, possibly required for efficient digestion of basic dietary residues that are necessary for mosquito reproduction and development. Importantly, we characterized the interaction between PCPBAe1 and DENV envelope (E) protein, virus-like particles, and infectious virions. We identified residues Asp18A, Glu19A, Glu85, Arg87, and Arg89 of PCPBAe1 are essential for interaction with DENV. PCPBAe1 maps to the dimeric interface of the E protein domains I/II (Lys64–Glu84, Val238–Val252, and Leu278–Leu287). Overall, our studies provide general insights into how the substrate-binding property of mosquito carboxypeptidases could be targeted to potentially control mosquito populations or proposes a mechanism by which PCPBAe1 binds to and inhibits DENV. |
| Databáze: | OpenAIRE |
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