Babesia bovis ligand-receptor interaction: AMA-1 contains small regions governing bovine erythrocyte binding

Laura Cuy-Chaparro, Michel David Bohórquez, Gabriela Arévalo-Pinzón, Jeimmy Johana Castañeda-Ramírez, Carlos Fernando Suárez, Laura Pabón, Diego Ordóñez, Gina Marcela Gallego-López, Carlos Esteban Suárez, Darwin Andrés Moreno-Pérez, Manuel Alfonso Patarroyo

Research output: Contribution to journalArticlepeer-review

Abstract

Apical membrane antigen 1 is a microneme protein which plays an indispensable role during Apicomplexa parasite invasion. The detailed mechanism of AMA-1 molecular interaction with its receptor on bovine erythrocytes has not been completely defined in Babesia bovis. This study was focused on identifying the minimum B. bovis AMA-1-derived regions governing specific and high-affinity binding to its target cells. Different approaches were used for detecting ama-1 locus genetic variability and natural selection signatures. The binding properties of twelve highly conserved 20-residue-long peptides were evaluated using a sensitive and specific binding assay based on radio-iodination. B. bovis AMA-1 ectodomain structure was modelled and refined using molecular modelling software. NetMHCIIpan software was used for calculating B-and T-cell epitopes. The B. bovis ama-1 gene had regions under functional constraint, having the highest negative selective pressure intensity in the Domain I encoding region. Interestingly, B. bovis AMA-1-DI (100YMQKFDIPRNHGSGIYVDLG119 and120GYESVGSKSYRMPVGKCPVV139 ) and DII (302CPMHPVRDAIFGKWSGGSCV321 )-derived peptides had high specificity interaction with erythrocytes and bound to a chymotrypsin and neuraminidase-treatment sensitive receptor. DI-derived peptides appear to be exposed on the protein’s surface and contain predicted B-and T-cell epitopes. These findings provide data (for the first-time) concerning B. bovis AMA-1 functional subunits which are important for establishing receptor-ligand interactions which could be used in synthetic vaccine development.

Original languageEnglish (US)
Article number714
Pages (from-to)1-15
Number of pages15
JournalInternational Journal of Molecular Sciences
Volume22
Issue number2
DOIs
StatePublished - Jan 2 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this