Abstract
Plasmodium falciparum (Pf) causes the most fatal form of malaria owing to its ability to cytoadhere in the microvasculature of various organs in the body. In addition to the Pf erythrocyte membrane protein 1 (PfEMP1) family that binds diverse host receptors, CX3CL1 binding proteins 1 and 2 (CBP1 and 2) also bind the endothelial chemokine ‘CX3CL1’ to effect cytoadhesion of parasite infected erythrocytes. CBP2 is a multifaceted protein that binds nucleic acids, Pf skeleton binding protein (PfSBP1) and ATP. ATP binding to the cytoplasmic domain of CBP2 (cCBP2) induces structural changes in the protein, and hints at its role in cell signalling. In this study, we have attempted to identify the ATP-binding pocket of CBP2 using an in silico approach. We have also delineated the type of interactions and amino acid residues that are likely to bind ATP. As CX3CL1 binding proteins are central to parasite biology, the obtained information is likely to form the basis for inhibitor and drug design against this molecule.
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References
Abdi A, Yu L, Goulding D, Rono MK, Bejon P, Choudhary J, Rayner J. (2017) Proteomic analysis of extracellular vesicles from a Plasmodium falciparum Kenyan clinical isolate defines a core parasite secretome. PMC. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583745/. Accessed 09 May, 2023
Bazan JF et al (1997) A new class of membrane-bound chemokine with a CX3C motif. Nature 385(6617):640–644. https://doi.org/10.1038/385640a0
Blisnick T, Betoulle MEM, Barale JC, Uzureau P, Berry L, Desroses S, Breton CB (2000) PfSBP1, a Maurer’s cleft Plasmodium falciparum protein, is associated with the eryth- rocyte skeleton. Mol Biochem Parasitol 111(1):107–121
Boddey JA, Moritz RL, Simpson RJ, Cowman AF (2009) Role of the plasmodium export element in trafficking parasite proteins to the infected erythrocyte. Traffic Cph Den 10(3):285–299. https://doi.org/10.1111/j.1600-0854.2008.00864.x
Chauhan JS, Mishra NK, Raghava GP (2009) Identification of ATP binding residues of a protein from its primary sequence. BMC Bioinform 10(1):434. https://doi.org/10.1186/1471-2105-10-434
Cowman AF, Healer J, Marapana D, Marsh K (2016) Malaria: biology and disease. Cell 167(3):610–624. https://doi.org/10.1016/j.cell.2016.07.055
Eberhardt J, Santos-Martins D, Tillack AF, Forli S (2021) AutoDock Vina 1.2.0: new docking methods, expanded force field, and python bindings. J Chem Inf Model 61(8):3891–3898. https://doi.org/10.1021/acs.jcim.1c00203
Fong AM et al (1998) Fractalkine and CX3CR1 mediate a novel mechanism of leukocyte capture, firm adhesion, and activation under physiologic flow. J Exp Med 188(8):1413–1419. https://doi.org/10.1084/jem.188.8.1413
Hatabu T, Kawazu SI, Aikawa M, Kano S (2003) Binding of Plasmodium falciparum-infected erythrocytes to the membrane-bound form of Fractalkine/CX3CL1. Proc Natl Acad Sci USA 100(26):15942–15946. https://doi.org/10.1073/pnas.2534560100
Hermand P, Cicéron L, Pionneau C, Vaquero C, Combadière C, Deterre P (2016) Plasmodium falciparum proteins involved in cytoadherence of infected erythrocytes to chemokine CX3CL1. Sci Rep. https://doi.org/10.1038/srep33786
Honorato Rodrigo V, Koukos Panagiotis I, Jiménez-García Brian, Tsaregorodtsev Andrei, Verlato Marco, Giachetti Andrea, Rosato Antonio, Bonvin Alexandre MJJ (2021) Structural biology in the clouds: the WeNMR-EOSC ecosystem. Front Mol Biosci 8:729513. https://doi.org/10.3389/fmolb.2021.729513/full
Hora R, Kapoor P, Thind KK, Mishra PC (2016) Cerebral malaria—clinical manifestations and pathogenesis. Metab Brain Dis 31(2):225–237. https://doi.org/10.1007/s11011-015-9787-5
Hossain MJ et al (2010) Plasmodium falciparum Tudor Staphylococcal Nuclease interacting proteins suggest its role in nuclear as well as splicing processes. Gene 468(1–2):48–57. https://doi.org/10.1016/j.gene.2010.08.004
Hu J, Li Y, Zhang Y, Yu D-J (2018) ATPbind: accurate protein–ATP binding site prediction by combining sequence-profiling and structure-based comparisons. J Chem Inf Model 58(2):501–510. https://doi.org/10.1021/acs.jcim.7b00397
Jones BA, Beamer M, Ahmed S (2010) Fractalkine/CX3CL1: A Potential New Target for Inflammatory Diseases. Mol Interv 10(5):263–270. https://doi.org/10.1124/mi.10.5.3
Jumper J et al (2021) Highly accurate protein structure prediction with AlphaFold. Nature. https://doi.org/10.1038/s41586-021-03819-2
Laskowski RA, Swindells MB (2011) LigPlot+: multiple ligand–protein interaction diagrams for drug discovery. J Chem Inf Model 51(10):2778–2786. https://doi.org/10.1021/ci200227u
Laskowski RA, MacArthur MW, Moss DS, Thornton JM (1993) PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Crystallogr. https://doi.org/10.1107/S0021889892009944
Maas SLN, Breakefield XO, Weaver AM (2017) Extracellular vesicles: unique intercellular delivery vehicles. Trends Cell Biol 27(3):172–188. https://doi.org/10.1016/j.tcb.2016.11.003
Maier AG et al (2008) Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes. Cell 134(1):48–61. https://doi.org/10.1016/j.cell.2008.04.051
Mantel P-Y et al (2013) Malaria-infected erythrocyte-derived microvesicles mediate cellular communication within the parasite population and with the host immune system. Cell Host Microbe 13(5):521–534. https://doi.org/10.1016/j.chom.2013.04.009
Marti M, Good RT, Rug M, Knuepfer E, Cowman AF (2004) Targeting malaria virulence and remodeling proteins to the host erythrocyte. Science 306(5703):1930–1933. https://doi.org/10.1126/science.1102452
Maxwell A, Lawson DM (2003) The ATP-binding site of type II topoisomerases as a target for antibacterial drugs. Curr Top Med Chem 3(3):283–303. https://doi.org/10.2174/1568026033452500
Mbengue A et al (2015) New export pathway in plasmodium falciparum-infected erythrocytes: role of the parasite group II chaperonin, PfTRiC. Traffic 16(5):461–475. https://doi.org/10.1111/tra.12266
McMillan PJ et al (2013) Spatial and temporal mapping of the PfEMP1 export pathway in Plasmodium falciparum. Cell Microbiol 15(8):1401–1418. https://doi.org/10.1111/cmi.12125
Mohandas N, An X (2012) Malaria and human red blood cells. Med Microbiol Immunol (Berl) 201(4):593–598. https://doi.org/10.1007/s00430-012-0272-z
Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera—a visualization system for exploratory research and analysis. J Comput Chem. https://doi.org/10.1002/jcc.20084
PlasmoDB. https://plasmodb.org/plasmo/app. Accessed 9 May, 2023.
Regev-Rudzki N, Wilson DW, Carvalho TG, Sisquella X, Coleman BM, Rug M, Bursac D, Angrisano F, Gee M, Hill AF, Baum J (201) Cell–cell communication between malaria-infected red blood cells via exosome-like vesicles. ScienceDirect
Rowe JA, Claessens A, Corrigan RA, Arman M (2009) Adhesion of Plasmodium falciparum-infected erythrocytes to human cells: molecular mechanisms and therapeutic implications. Expert Rev Mol Med 11:e16. https://doi.org/10.1017/S1462399409001082
Sam-Yellowe TY (2009) The role of the Maurer’s clefts in protein transport in Plasmodium falciparum. Trends Parasitol 25(6):277–284. https://doi.org/10.1016/j.pt.2009.03.009
Sargeant TJ et al (2006) Lineage-specific expansion of proteins exported to erythrocytes in malaria parasites. Genome Biol 7(2):R12. https://doi.org/10.1186/gb-2006-7-2-r12
Saxena R, Kaur J, Hora R, Singh P, Singh V, Mishra PC (2019) CX3CL1 binding protein-2 (CBP2) of Plasmodium falciparum binds nucleic acids. Int J Biol Macromol 138:996–1005. https://doi.org/10.1016/j.ijbiomac.2019.07.178
Silvestrini F et al (2010) Protein export marks the early phase of gametocytogenesis of the human malaria parasite Plasmodium falciparum. Mol Cell Proteom 9(7):1437–1448
Sleebs BE et al (2014) Inhibition of Plasmepsin V activity demonstrates its essential role in protein export, PfEMP1 display, and survival of malaria parasites. PLoS Biol 12(7):e1001897. https://doi.org/10.1371/journal.pbio.1001897
Soni R, Sharma D, Rai P, Sharma B, Bhatt TK (2017) Signaling strategies of malaria parasite for its survival, proliferation, and infection during erythrocytic stage. Front Immunol 8:349
White NJ (2017) Malaria parasite clearance. Malar J 16(1):88. https://doi.org/10.1186/s12936-017-1731-1
Ye W, Chew M, Hou J, Lai F, Leopold SJ, Loo HL, Ghose A, Dutta AK, Chen Q, Ooi EE, White NJ (2018) Microvesicles from malaria-infected red blood cells activate natural killer cells via MDA5 pathway. PLOS Pathogens. https://doi.org/10.1371/journal.ppat.1007298
Yoshie O, Imai T, Nomiyama H (2001) Chemokines in immunity. In: F. Dixon J (eds) Advances in immunology, vol 78. Academic Press, Cambridge, pp 57–110. https://doi.org/10.1016/S0065-2776(01)78002-9
Zhang M et al (2018) Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis. Science. https://doi.org/10.1126/science.aap7847
Acknowledgements
RK was receiving scholarship from DBT, Government of India. SK is a DBT-SRF. The laboratories of PCM and RH are funded by UGC-DAE and were earlier funded by DBT, RUSA and DST, Government of India.
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RK and SK were involved in experimentation. RK, RH and PCM wrote manuscript. RH and PCM were supervised the study. All authors read and reviewed the manuscript.
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Kumari, R., Kaur, S., Hora, R. et al. Investigating the ATP-binding pocket of CX3CL1-binding protein 2 using in silico approach. J Proteins Proteom (2024). https://doi.org/10.1007/s42485-024-00133-z
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DOI: https://doi.org/10.1007/s42485-024-00133-z