Identification of Exported Plasmodium falciparum Proteins That Bind to the Erythrocyte Cytoskeleton

Shakya, Bikash; Kilili, Geoffrey Kimiti; Wang, Ling; Nakayasu, Ernesto S.; LaCount, Douglas J.

doi:10.3390/microorganisms10071438

Identification of Exported Plasmodium falciparum Proteins That Bind to the Erythrocyte Cytoskeleton

Journal Article · Sat Jul 16 00:00:00 EDT 2022 · Microorganisms

DOI:https://doi.org/10.3390/microorganisms10071438· OSTI ID:2471606

^[1]; Kilili, Geoffrey Kimiti ^[1]; Wang, Ling ^[1]; ^[2]; ^[1]

Purdue University, West Lafayette, IN (United States)
Purdue University, West Lafayette, IN (United States); Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Plasmodium proteins are exported to the erythrocyte cytoplasm to create an environment that supports parasite replication. Although hundreds of proteins are predicted to be exported through Plasmodium export element (PEXEL)-dependent and -independent mechanisms, the functions of exported proteins are largely uncharacterized. In this study, we used a biochemical screening approach to identify putative exported P. falciparum proteins that bound to inside-out vesicles prepared from erythrocytes. Out of 69 P. falciparum PEXEL-motif proteins tested, 18 bound to inside-out vesicles (IOVs) in two or more independent assays. Using co-affinity purifications followed by mass spectrometry, pairwise co-purification experiments, and the split-luciferase assay, we identified 31 putative protein–protein interactions between erythrocyte cytoskeletal proteins and predicted exported P. falciparum proteins. We further showed that PF3D7_1401600 binds to the spectrin-binding domain of erythrocyte ankyrin via its MESA erythrocyte cytoskeleton binding (MEC) motif and to the N-terminal domains of ankyrin and 4.1R through a fragment that required an intact Plasmodium helical interspersed sub-telomeric (PHIST) domain. Introduction of PF3D7_1401600 into erythrocyte ghosts increased retention in the microsphiltration assay, consistent with previous data that reported a reduction of rigidity in red blood cells infected with PF3D7_1401600-deficient parasites.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF); National Institutes of Health (NIH)

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 2471606

Journal Information:: Microorganisms, Journal Name: Microorganisms Journal Issue: 7 Vol. 10; ISSN 2076-2607

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

References (63)

One-Step Purification of Recombinant Proteins Using a Nanomolar-Affinity Streptavidin-Binding Peptide, the SBP-Tag Keefe, Anthony D.; Wilson, David S.; Seelig, Burckhard Protein Expression and Purification, Vol. 23, Issue 3 https://doi.org/10.1006/prep.2001.1515	journal	December 2001
MESA is a Plasmodium falciparum phosphoprotein associated with the erythrocyte membrane skeleton Coppel, R.; Lustigman, S.; Murray, L. Molecular and Biochemical Parasitology, Vol. 31, Issue 3 https://doi.org/10.1016/0166-6851(88)90152-1	journal	December 1988
The mature-parasite-infected erythrocyte surface antigen (MESA) of Plasmodium falciparum associates with the erythrocyte membrane skeletal protein, band 4.1 Lustigman, S.; Anders, R.; Brown, G. Molecular and Biochemical Parasitology, Vol. 38, Issue 2 https://doi.org/10.1016/0166-6851(90)90029-L	journal	January 1990
The ring-infected erythrocyte surface antigen protein of Plasmodium falciparum is phosphorylated upon association with the host cell membrane Foley, Micheal; Murray, Leecia J.; Anders, Robin F. Molecular and Biochemical Parasitology, Vol. 38, Issue 1 https://doi.org/10.1016/0166-6851(90)90206-2	journal	January 1990
The Plasmodium falciparum protein RESA interacts with the erythrocyte cytoskeleton and modifies erythrocyte thermal stability Da Silva, Elizabeth; Foley, Michael; Dluzewski, Anton R. Molecular and Biochemical Parasitology, Vol. 66, Issue 1 https://doi.org/10.1016/0166-6851(94)90036-1	journal	July 1994
Plasmid construction by homologous recombination in yeast Ma, Hong; Kunes, Sam; Schatz, Peter J. Gene, Vol. 58, Issue 2-3 https://doi.org/10.1016/0378-1119(87)90376-3	journal	January 1987
The membrane-binding domain of ankyrin contains four independently folded subdomains, each comprised of six ankyrin repeats. Michaely, P.; Bennett, V. Journal of Biological Chemistry, Vol. 268, Issue 30 https://doi.org/10.1016/S0021-9258(18)41584-0	journal	October 1993
Effect of red cell membrane binding on the catalytic activity of glyceraldehyde-3-phosphate dehydrogenase. Tsai, I. H.; Murthy, S. N.; Steck, T. L. Journal of Biological Chemistry, Vol. 257, Issue 3 https://doi.org/10.1016/S0021-9258(19)68212-8	journal	February 1982
Plasmodium falciparum erythrocyte membrane protein 1 is anchored to the actin–spectrin junction and knob-associated histidine-rich protein in the erythrocyte skeleton Oh, S. Steven; Voigt, Sabine; Fisher, Derek Molecular and Biochemical Parasitology, Vol. 108, Issue 2 https://doi.org/10.1016/S0166-6851(00)00227-9	journal	May 2000
Plasmodium falciparum histidine-rich protein 1 associates with the band 3 binding domain of ankyrin in the infected red cell membrane Magowan, Cathleen; Nunomura, Wataru; Waller, Karena L. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Vol. 1502, Issue 3 https://doi.org/10.1016/S0925-4439(00)00069-7	journal	November 2000
Reduced microcirculatory flow in severe falciparum malaria: pathophysiology and electron-microscopic pathology Dondorp, Arjen M.; Pongponratn, Emsri; White, Nicholas J. Acta Tropica, Vol. 89, Issue 3 https://doi.org/10.1016/j.actatropica.2003.10.004	journal	February 2004
Interactions of Plasmodium falciparum erythrocyte membrane protein 3 with the red blood cell membrane skeleton Waller, Karena L.; Stubberfield, Lisa M.; Dubljevic, Valentina Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1768, Issue 9 https://doi.org/10.1016/j.bbamem.2007.04.027	journal	September 2007
Interaction of the exported malaria protein Pf332 with the red blood cell membrane skeleton Waller, Karena L.; Stubberfield, Lisa M.; Dubljevic, Valentina Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1798, Issue 5 https://doi.org/10.1016/j.bbamem.2010.01.018	journal	May 2010
Interaction of Plasmodium falciparum knob-associated histidine-rich protein (KAHRP) with erythrocyte ankyrin R is required for its attachment to the erythrocyte membrane Weng, Haibo; Guo, Xinhua; Papoin, Julien Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1838, Issue 1 https://doi.org/10.1016/j.bbamem.2013.09.014	journal	January 2014
Interactions between Plasmodium falciparum skeleton-binding protein 1 and the membrane skeleton of malaria-infected red blood cells Kats, Lev M.; Proellocks, Nicholas I.; Buckingham, Donna W. Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol. 1848, Issue 7 https://doi.org/10.1016/j.bbamem.2015.03.038	journal	July 2015
Exported Proteins Required for Virulence and Rigidity of Plasmodium falciparum-Infected Human Erythrocytes Maier, Alexander G.; Rug, Melanie; O'Neill, Matthew T. Cell, Vol. 134, Issue 1 https://doi.org/10.1016/j.cell.2008.04.051	journal	July 2008
SAINTexpress: Improvements and additional features in Significance Analysis of INTeractome software Teo, Guoci; Liu, Guomin; Zhang, Jianping Journal of Proteomics, Vol. 100 https://doi.org/10.1016/j.jprot.2013.10.023	journal	April 2014
LANCL1, an erythrocyte protein recruited to the Maurer's clefts during Plasmodium falciparum development Blisnick, Thierry; Vincensini, Laetitia; Barale, Jean Christophe Molecular and Biochemical Parasitology, Vol. 141, Issue 1 https://doi.org/10.1016/j.molbiopara.2005.01.013	journal	May 2005
The Plasmodium falciparum exported protein PF3D7_0402000 binds to erythrocyte ankyrin and band 4.1 Shakya, Bikash; Penn, Wesley D.; Nakayasu, Ernesto S. Molecular and Biochemical Parasitology, Vol. 216 https://doi.org/10.1016/j.molbiopara.2017.06.002	journal	September 2017
The Plasmodium falciparum MESA erythrocyte cytoskeleton-binding (MEC) motif binds to erythrocyte ankyrin Kilili, Geoffrey Kimiti; Shakya, Bikash; Dolan, Patrick T. Molecular and Biochemical Parasitology, Vol. 231 https://doi.org/10.1016/j.molbiopara.2019.111189	journal	July 2019
Defining the Essential Exportome of the Malaria Parasite Jonsdottir, Thorey K.; Gabriela, Mikha; Crabb, Brendan S. Trends in Parasitology, Vol. 37, Issue 7 https://doi.org/10.1016/j.pt.2021.04.009	journal	July 2021
Combinatorial Library Screening for Developing an Improved Split-Firefly Luciferase Fragment-Assisted Complementation System for Studying Protein−Protein Interactions Paulmurugan, Ramasamy; Gambhir, Sanjiv S. Analytical Chemistry, Vol. 79, Issue 6 https://doi.org/10.1021/ac062053q	journal	February 2007
MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification Cox, Jürgen; Mann, Matthias Nature Biotechnology, Vol. 26, Issue 12 https://doi.org/10.1038/nbt.1511	journal	November 2008
An experimentally derived confidence score for binary protein-protein interactions Braun, Pascal; Tasan, Murat; Dreze, Matija Nature Methods, Vol. 6, Issue 1 https://doi.org/10.1038/nmeth.1281	journal	December 2008
SAINT: probabilistic scoring of affinity purification–mass spectrometry data Choi, Hyungwon; Larsen, Brett; Lin, Zhen-Yuan Nature Methods, Vol. 8, Issue 1 https://doi.org/10.1038/nmeth.1541	journal	December 2010
The CRAPome: a contaminant repository for affinity purification–mass spectrometry data Mellacheruvu, Dattatreya; Wright, Zachary; Couzens, Amber L. Nature Methods, Vol. 10, Issue 8 https://doi.org/10.1038/nmeth.2557	journal	July 2013
Plasmodium species: master renovators of their host cells de Koning-Ward, Tania F.; Dixon, Matthew W. A.; Tilley, Leann Nature Reviews Microbiology, Vol. 14, Issue 8 https://doi.org/10.1038/nrmicro.2016.79	journal	July 2016
Malaria parasite proteins that remodel the host erythrocyte Maier, Alexander G.; Cooke, Brian M.; Cowman, Alan F. Nature Reviews Microbiology, Vol. 7, Issue 5 https://doi.org/10.1038/nrmicro2110	journal	May 2009
Moving in and renovating: exporting proteins from Plasmodium into host erythrocytes Goldberg, Daniel E.; Cowman, Alan F. Nature Reviews Microbiology, Vol. 8, Issue 9 https://doi.org/10.1038/nrmicro2420	journal	September 2010
Pf155/RESA protein influences the dynamic microcirculatory behavior of ring-stage Plasmodium falciparum infected red blood cells Diez-Silva, Monica; Park, YongKeun; Huang, Sha Scientific Reports, Vol. 2, Issue 1 https://doi.org/10.1038/srep00614	journal	August 2012
Mapping of glycolytic enzyme-binding sites on human erythrocyte band 3 Chu, Haiyan; Low, Philip S. Biochemical Journal, Vol. 400, Issue 1 https://doi.org/10.1042/BJ20060792	journal	October 2006
Effect of plasmodial RESA protein on deformability of human red blood cells harboring Plasmodium falciparum Mills, J. P.; Diez-Silva, M.; Quinn, D. J. Proceedings of the National Academy of Sciences, Vol. 104, Issue 22 https://doi.org/10.1073/pnas.0703433104	journal	May 2007
Plasmodium falciparum erythrocyte membrane protein 1 is a parasitized erythrocyte receptor for adherence to CD36, thrombospondin, and intercellular adhesion molecule 1. Baruch, D. I.; Gormely, J. A.; Ma, C. Proceedings of the National Academy of Sciences, Vol. 93, Issue 8 https://doi.org/10.1073/pnas.93.8.3497	journal	April 1996
Modulation of Band 3-Ankyrin Interaction by Protein 4.1 An, Xiu-Li; Takakuwa, Yuichi; Nunomura, Wataru Journal of Biological Chemistry, Vol. 271, Issue 52 https://doi.org/10.1074/jbc.271.52.33187	journal	December 1996
Defining the Minimal Domain of the Plasmodium falciparum Protein MESA Involved in the Interaction with the Red Cell Membrane Skeletal Protein 4.1 Bennett, Billy J.; Mohandas, Narla; Coppel, Ross L. Journal of Biological Chemistry, Vol. 272, Issue 24 https://doi.org/10.1074/jbc.272.24.15299	journal	June 1997
Identification of the Components of a Glycolytic Enzyme Metabolon on the Human Red Blood Cell Membrane Puchulu-Campanella, Estela; Chu, Haiyan; Anstee, David J. Journal of Biological Chemistry, Vol. 288, Issue 2 https://doi.org/10.1074/jbc.M112.428573	journal	November 2012
Structural and Functional Studies of Interaction between Plasmodium falciparum Knob-associated Histidine-rich Protein (KAHRP) and Erythrocyte Spectrin Pei, Xinhong; An, Xiuli; Guo, Xinhua Journal of Biological Chemistry, Vol. 280, Issue 35 https://doi.org/10.1074/jbc.M505298200	journal	September 2005
Plasmodium falciparum Erythrocyte Membrane Protein 3 (PfEMP3) Destabilizes Erythrocyte Membrane Skeleton Pei, Xinhong; Guo, Xinhua; Coppel, Ross Journal of Biological Chemistry, Vol. 282, Issue 37 https://doi.org/10.1074/jbc.M701612200	journal	September 2007
A Physical Interaction Network of Dengue Virus and Human Proteins Khadka, Sudip; Vangeloff, Abbey D.; Zhang, Chaoying Molecular & Cellular Proteomics, Vol. 10, Issue 12 https://doi.org/10.1074/mcp.M111.012187	journal	December 2011
Home Improvements: How the Malaria Parasite Makes the Red Blood Cell Home Sweet Home Starnes, G. L.; Waters, A. P. Journal of Molecular Cell Biology, Vol. 2, Issue 1 https://doi.org/10.1093/jmcb/mjp024	journal	October 2009
A lysine‐rich membrane‐associated PHISTb protein involved in alteration of the cytoadhesive properties of Plasmodium falciparum ‐infected red blood cells Proellocks, Nicholas I.; Herrmann, Susann; Buckingham, Donna W. The FASEB Journal, Vol. 28, Issue 7 https://doi.org/10.1096/fj.14-250399	journal	March 2014
Plasmodium falciparum Plasmodiumhelical interspersed subtelomeric proteins contribute to cytoadherence and anchorP. falciparumerythrocyte membrane protein 1 to the host cell cytoskeleton Oberli, Alexander; Zurbrügg, Laura; Rusch, Sebastian Cellular Microbiology, Vol. 18, Issue 10 https://doi.org/10.1111/cmi.12583	journal	April 2016
Analysis of structure and function of the giant protein Pf332 in Plasmodium falciparum Hodder, Anthony N.; Maier, Alexander G.; Rug, Melanie Molecular Microbiology, Vol. 71, Issue 1 https://doi.org/10.1111/j.1365-2958.2008.06508.x	journal	December 2008
New insights into the blood-stage transcriptome of Plasmodium falciparum using RNA-Seq Otto, Thomas D.; Wilinski, Daniel; Assefa, Sammy Molecular Microbiology, Vol. 76, Issue 1 https://doi.org/10.1111/j.1365-2958.2009.07026.x	journal	April 2010
Novel Plasmodium falciparum Maurer's clefts protein families implicated in the release of infectious merozoites Mbengue, Alassane; Audiger, Nicolas; Vialla, Emilie Molecular Microbiology, Vol. 88, Issue 2 https://doi.org/10.1111/mmi.12193	journal	March 2013
The Plasmodium falciparum exportome contains non‐canonical PEXEL/HT proteins Schulze, Jana; Kwiatkowski, Marcel; Borner, Janus Molecular Microbiology, Vol. 97, Issue 2 https://doi.org/10.1111/mmi.13024	journal	May 2015
Targeting Malaria Virulence and Remodeling Proteins to the Host Erythrocyte Marti, M. Science, Vol. 306, Issue 5703 https://doi.org/10.1126/science.1102452	journal	December 2004
A Host-Targeting Signal in Virulence Proteins Reveals a Secretome in Malarial Infection Hiller, N. L. Science, Vol. 306, Issue 5703 https://doi.org/10.1126/science.1102737	journal	December 2004
Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis Zhang, Min; Wang, Chengqi; Otto, Thomas D. Science, Vol. 360, Issue 6388 https://doi.org/10.1126/science.aap7847	journal	May 2018
An Erythrocyte Cytoskeleton-Binding Motif in Exported Plasmodium falciparum Proteins Kilili, Geoffrey K.; LaCount, Douglas J. Eukaryotic Cell, Vol. 10, Issue 11 https://doi.org/10.1128/EC.05180-11	journal	September 2011
Host Cytoskeleton Remodeling throughout the Blood Stages of Plasmodium falciparum Warncke, Jan D.; Beck, Hans-Peter Microbiology and Molecular Biology Reviews, Vol. 83, Issue 4 https://doi.org/10.1128/MMBR.00013-19	journal	November 2019
Plasmodium Nesting: Remaking the Erythrocyte from the Inside Out Boddey, Justin A.; Cowman, Alan F. Annual Review of Microbiology, Vol. 67, Issue 1 https://doi.org/10.1146/annurev-micro-092412-155730	journal	September 2013
The role of KAHRP domains in knob formation and cytoadherence of P falciparum-infected human erythrocytes Rug, Melanie; Prescott, Stuart W.; Fernandez, Kate M. Blood, Vol. 108, Issue 1 https://doi.org/10.1182/blood-2005-11-4624	journal	July 2006
The ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum stabilizes spectrin tetramers and suppresses further invasion Pei, Xinhong; Guo, Xinhua; Coppel, Ross Blood, Vol. 110, Issue 3 https://doi.org/10.1182/blood-2007-02-076919	journal	August 2007
Functional alteration of red blood cells by a megadalton protein of Plasmodium falciparum Glenister, Fiona K.; Fernandez, Kate M.; Kats, Lev M. Blood, Vol. 113, Issue 4 https://doi.org/10.1182/blood-2008-05-157735	journal	January 2009
Plasmodium falciparum STEVOR proteins impact erythrocyte mechanical properties Sanyal, Sohini; Egée, Stéphane; Bouyer, Guillaume Blood, Vol. 119, Issue 2 https://doi.org/10.1182/blood-2011-08-370734	journal	January 2012
Anatomy of the red cell membrane skeleton: unanswered questions Lux, Samuel E. Blood, Vol. 127, Issue 2 https://doi.org/10.1182/blood-2014-12-512772	journal	January 2016
Contribution of the band 3-ankyrin interaction to erythrocyte membrane mechanical stability Low, Ps; Willardson, Bm; Mohandas, N. Blood, Vol. 77, Issue 7 https://doi.org/10.1182/blood.V77.7.1581.1581	journal	April 1991
A member of the Plasmodium falciparum PHIST family binds to the erythrocyte cytoskeleton component band 4.1 Parish, Lindsay A.; Mai, Deborah W.; Jones, Matthew L. Malaria Journal, Vol. 12, Issue 1 https://doi.org/10.1186/1475-2875-12-160	journal	January 2013
Correction: The Malaria Secretome: From Algorithms to Essential Function in Blood Stage Infection van Ooij, Christiaan; Tamez, Pamela; Bhattacharjee, Souvik PLoS Pathogens, Vol. 4, Issue 6 https://doi.org/10.1371/annotation/2b000375-e083-46ed-a44a-ff297e6c37d0	journal	June 2008
Erythrocyte G Protein as a Novel Target for Malarial Chemotherapy Murphy, Sean C.; Harrison, Travis; Hamm, Heidi E. PLoS Medicine, Vol. 3, Issue 12 https://doi.org/10.1371/journal.pmed.0030528	journal	December 2006
An Exported Heat Shock Protein 40 Associates with Pathogenesis-Related Knobs in Plasmodium falciparum Infected Erythrocytes Acharya, Pragyan; Chaubey, Shweta; Grover, Manish PLoS ONE, Vol. 7, Issue 9 https://doi.org/10.1371/journal.pone.0044605	journal	September 2012
Identification of New PNEPs Indicates a Substantial Non-PEXEL Exportome and Underpins Common Features in Plasmodium falciparum Protein Export Heiber, Arlett; Kruse, Florian; Pick, Christian PLoS Pathogens, Vol. 9, Issue 8 https://doi.org/10.1371/journal.ppat.1003546	journal	August 2013

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59 BASIC BIOLOGICAL SCIENCES
PF3D7_1401600
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ankyrin
band 4.1
cytoskeleton
erythrocyte
exported protein
host–pathogen interaction
microbiology
red blood cell

Identification of Exported Plasmodium falciparum Proteins That Bind to the Erythrocyte Cytoskeleton

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