Back to Search Start Over

Plasmodium falciparum rhoptry neck protein 4 has conserved regions mediating interactions with receptors on human erythrocytes and hepatocyte membrane

Authors :
Fredy A. Pulido-Quevedo
Gabriela Arévalo-Pinzón
Jeimmy J. Castañeda-Ramírez
Adriana Barreto-Santamaría
Manuel E. Patarroyo
Manuel A. Patarroyo
Source :
International Journal of Medical Microbiology, Vol 313, Iss 3, Pp 151579- (2023)
Publication Year :
2023
Publisher :
Elsevier, 2023.

Abstract

Plasmodium falciparum-related malaria represents a serious worldwide public health problem due to its high mortality rates. P. falciparum expresses rhoptry neck protein 4 (PfRON4) in merozoite and sporozoite rhoptries, it participates in tight junction-TJ formation via the AMA-1/RON complex and is refractory to complete genetic deletion. Despite this, which PfRON4 key regions interact with host cells remain unknown; such information would be useful for combating falciparum malaria. Thirty-two RON4 conserved region-derived peptides were chemically synthesised for determining and characterising PfRON4 regions having high host cell binding affinity (high activity binding peptides or HABPs). Receptor-ligand interaction/binding assays determined their specific binding capability, the nature of their receptors and their ability to inhibit in vitro parasite invasion. Peptides 42477, 42479, 42480, 42505 and 42513 had greater than 2% erythrocyte binding activity, whilst peptides 42477 and 42480 specifically bound to HepG2 membrane, both of them having micromolar and submicromolar range dissociation constants (Kd). Cell-peptide interaction was sensitive to treating erythrocytes with trypsin and/or chymotrypsin and HepG2 with heparinase I and chondroitinase ABC, suggesting protein-type (erythrocyte) and heparin and/or chondroitin sulphate proteoglycan receptors (HepG2) for PfRON4. Erythrocyte invasion inhibition assays confirmed HABPs’ importance during merozoite invasion. PfRON4 800–819 (42477) and 860–879 (42480) regions specifically interacted with host cells, thereby supporting their inclusion in a subunit-based, multi-antigen, multistage anti-malarial vaccine.

Details

Language :
English
ISSN :
14384221
Volume :
313
Issue :
3
Database :
Directory of Open Access Journals
Journal :
International Journal of Medical Microbiology
Publication Type :
Academic Journal
Accession number :
edsdoj.061a3332c23649e494f31f1d97dbe15f
Document Type :
article
Full Text :
https://doi.org/10.1016/j.ijmm.2023.151579