TY - JOUR
T1 - Receptor–ligand and parasite protein–protein interactions in Plasmodium vivax: Analysing rhoptry neck proteins 2 and 4
AU - Bermúdez, Maritza
AU - Arévalo-Pinzón, Gabriela
AU - Rubio, Laura
AU - Chaloin, Olivier
AU - Muller, Sylviane
AU - Curtidor, Hernando
AU - Patarroyo, Manuel Alfonso
N1 - Funding Information:
Departamento Administrativo de Ciencia, Tecnología e Innovación (Colciencias), Grant/ Award Number: RC#0309‐2013; Initiative of Excellence (IdEx); Laboratory of Excellence Medalis, Grant/Award Number: ANR‐10‐ LABX‐0034; French Centre National de la Recherche Scientifique (CNRS)
Funding Information:
We are grateful to Prof. Asif Mohmmed and Prof. Chetan E. Chitnis from the International Centre for Genetic Engineering and Biotechnology (New Delhi, India) for providing pRE4 and pHVDR22 plasmids. We would like to thank Dr. Bernardo Camacho and Dr. Ana María Perdomo from the Instituto Distrital de Ciencia, Biotecnología e Innovación en Salud (IDCBIS), for providing UCB and also Jason Garry for translating this manuscript. This research was financed by the Colombian Science, Technology, and Innovation Department (COLCIENCIAS) through the contract RC#0309‐2013 and in part, by the French Centre National de la Recherche Scientifique (CNRS), the Laboratory of Excellence Medalis (ANR‐10‐LABX‐0034), Initiative of Excellence (IdEx), Strasbourg University, France. GAP was financed by COLCIENCIAS' National Call for PhD Studies in Colombia (No. 567). M. B. was financed by the “High level human talent training” project, approved by the Colombian General Royalties System's (GRS) “Science, Technology and Innovation Fund” (CTeI) BPIN 2013000100103, Tolima Department's Governor's Office and by the Universidad del Tolima, Colombia. The sponsors had no role in study design or data collection, analysis, and/or interpretation.
Publisher Copyright:
© 2018 John Wiley & Sons Ltd
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2018/7
Y1 - 2018/7
N2 - Elucidating receptor–ligand and protein–protein interactions represents an attractive alternative for designing effective Plasmodium vivax control methods. This article describes the ability of P. vivax rhoptry neck proteins 2 and 4 (RON2 and RON4) to bind to human reticulocytes. Biochemical and cellular studies have shown that two PvRON2- and PvRON4-derived conserved regions specifically interact with protein receptGuardarors on reticulocytes marked by the CD71 surface transferrin receptor. Mapping each protein fragment's binding region led to defining the specific participation of two 20 amino acid-long regions selectively competing for PvRON2 and PvRON4 binding to reticulocytes. Binary interactions between PvRON2 (ligand) and other parasite proteins, such as PvRON4, PvRON5, and apical membrane antigen 1 (AMA1), were evaluated and characterised by surface plasmon resonance. The results revealed that both PvRON2 cysteine-rich regions strongly interact with PvAMA1 Domains II and III (equilibrium constants in the nanomolar range) and at a lower extent with the complete PvAMA1 ectodomain and Domains I and II. These results strongly support that these proteins participate in P. vivax's complex invasion process, thus providing new pertinent targets for blocking P. vivax merozoites' specific entry to their target cells.
AB - Elucidating receptor–ligand and protein–protein interactions represents an attractive alternative for designing effective Plasmodium vivax control methods. This article describes the ability of P. vivax rhoptry neck proteins 2 and 4 (RON2 and RON4) to bind to human reticulocytes. Biochemical and cellular studies have shown that two PvRON2- and PvRON4-derived conserved regions specifically interact with protein receptGuardarors on reticulocytes marked by the CD71 surface transferrin receptor. Mapping each protein fragment's binding region led to defining the specific participation of two 20 amino acid-long regions selectively competing for PvRON2 and PvRON4 binding to reticulocytes. Binary interactions between PvRON2 (ligand) and other parasite proteins, such as PvRON4, PvRON5, and apical membrane antigen 1 (AMA1), were evaluated and characterised by surface plasmon resonance. The results revealed that both PvRON2 cysteine-rich regions strongly interact with PvAMA1 Domains II and III (equilibrium constants in the nanomolar range) and at a lower extent with the complete PvAMA1 ectodomain and Domains I and II. These results strongly support that these proteins participate in P. vivax's complex invasion process, thus providing new pertinent targets for blocking P. vivax merozoites' specific entry to their target cells.
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U2 - 10.1111/cmi.12835
DO - 10.1111/cmi.12835
M3 - Research Article
C2 - 29488316
AN - SCOPUS:85044402275
SN - 1462-5814
VL - 20
JO - Cellular Microbiology
JF - Cellular Microbiology
IS - 7
M1 - e12835
ER -