Plasmepsin v licenses Plasmodium proteins for export into the host erythrocyte

Ilaria Russo; Shalon Babbitt; Vasant Muralidharan; Tamira Butler; Anna Oksman; Daniel E. Goldberg

doi:10.1038/nature08726

Plasmepsin v licenses Plasmodium proteins for export into the host erythrocyte

Ilaria Russo, Shalon Babbitt, Vasant Muralidharan, Tamira Butler, Anna Oksman, Daniel E. Goldberg

Research output: Contribution to journal › Article › peer-review

Abstract

During their intraerythrocytic development, malaria parasites export hundreds of proteins to remodel their host cell. Nutrient acquisition, cytoadherence and antigenic variation are among the key virulence functions effected by this erythrocyte takeover. Proteins destined for export are synthesized in the endoplasmic reticulum (ER) and cleaved at a conserved (PEXEL) motif, which allows translocation into the host cell via an ATP-driven translocon called the PTEX complex. We report that plasmepsin V, an ER aspartic protease with distant homology to the mammalian processing enzyme BACE, recognizes the PEXEL motif and cleaves it at the correct site. This enzyme is essential for parasite viability and ER residence is essential for its function. We propose that plasmepsin V is the PEXEL protease and is an attractive enzyme for antimalarial drug development. © 2010 Macmillan Publishers Limited. All rights reserved.

Original language	English
Pages (from-to)	632-636
Number of pages	4
Journal	Nature
Volume	463
Issue number	7281
DOIs	https://doi.org/10.1038/nature08726
Publication status	Published - 4 Feb 2010

Keywords

Amino Acid Motifs
Animals
Antimalarials/pharmacology
Aspartic Acid Endopeptidases/antagonists &
inhibitors/chemistry/genetics/*metabolism
Biocatalysis/drug effects
Endoplasmic Reticulum/enzymology/metabolism
Erythrocytes/cytology/*metabolism/parasitology
Genes, Dominant
Genes, Essential
HIV Protease Inhibitors/pharmacology
Humans
Malaria, Falciparum/*blood/metabolism/*parasitology/pathology
Multiprotein Complexes/metabolism
Pepstatins/pharmacology
Phenotype
Plasmids/genetics
Plasmodium falciparum/enzymology/genetics/*metabolism/pathogenicity
Protein Binding
Protein Sorting Signals
Protein Structure, Tertiary
Protein Transport
Proteomics
Protozoan Proteins/chemistry/*metabolism
Substrate Specificity

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/nature08726

http://www.ncbi.nlm.nih.gov/pubmed/20130644

Cite this

@article{cd7273c7092c46589dd3c5200236fdd0,

title = "Plasmepsin v licenses Plasmodium proteins for export into the host erythrocyte",

abstract = "During their intraerythrocytic development, malaria parasites export hundreds of proteins to remodel their host cell. Nutrient acquisition, cytoadherence and antigenic variation are among the key virulence functions effected by this erythrocyte takeover. Proteins destined for export are synthesized in the endoplasmic reticulum (ER) and cleaved at a conserved (PEXEL) motif, which allows translocation into the host cell via an ATP-driven translocon called the PTEX complex. We report that plasmepsin V, an ER aspartic protease with distant homology to the mammalian processing enzyme BACE, recognizes the PEXEL motif and cleaves it at the correct site. This enzyme is essential for parasite viability and ER residence is essential for its function. We propose that plasmepsin V is the PEXEL protease and is an attractive enzyme for antimalarial drug development. {\textcopyright} 2010 Macmillan Publishers Limited. All rights reserved.",

keywords = "Amino Acid Motifs, Animals, Antimalarials/pharmacology, Aspartic Acid Endopeptidases/antagonists &, inhibitors/chemistry/genetics/*metabolism, Biocatalysis/drug effects, Endoplasmic Reticulum/enzymology/metabolism, Erythrocytes/cytology/*metabolism/parasitology, Genes, Dominant, Genes, Essential, HIV Protease Inhibitors/pharmacology, Humans, Malaria, Falciparum/*blood/metabolism/*parasitology/pathology, Multiprotein Complexes/metabolism, Pepstatins/pharmacology, Phenotype, Plasmids/genetics, Plasmodium falciparum/enzymology/genetics/*metabolism/pathogenicity, Protein Binding, Protein Sorting Signals, Protein Structure, Tertiary, Protein Transport, Proteomics, Protozoan Proteins/chemistry/*metabolism, Substrate Specificity",

author = "Ilaria Russo and Shalon Babbitt and Vasant Muralidharan and Tamira Butler and Anna Oksman and Goldberg, {Daniel E.}",

note = "Russo, Ilaria Babbitt, Shalon Muralidharan, Vasant Butler, Tamira Oksman, Anna Goldberg, Daniel E AI-047798/AI/NIAID NIH HHS/ R01 AI047798/AI/NIAID NIH HHS/ R01 AI047798-10/AI/NIAID NIH HHS/ Howard Hughes Medical Institute/ England Nature. 2010 Feb 4;463(7281):632-6. doi: 10.1038/nature08726.",

year = "2010",

month = feb,

day = "4",

doi = "10.1038/nature08726",

language = "English",

volume = "463",

pages = "632--636",

journal = "Nature",

issn = "0028-0836",

publisher = "Springer Nature",

number = "7281",

}

TY - JOUR

T1 - Plasmepsin v licenses Plasmodium proteins for export into the host erythrocyte

AU - Russo, Ilaria

AU - Babbitt, Shalon

AU - Muralidharan, Vasant

AU - Butler, Tamira

AU - Oksman, Anna

AU - Goldberg, Daniel E.

N1 - Russo, Ilaria Babbitt, Shalon Muralidharan, Vasant Butler, Tamira Oksman, Anna Goldberg, Daniel E AI-047798/AI/NIAID NIH HHS/ R01 AI047798/AI/NIAID NIH HHS/ R01 AI047798-10/AI/NIAID NIH HHS/ Howard Hughes Medical Institute/ England Nature. 2010 Feb 4;463(7281):632-6. doi: 10.1038/nature08726.

PY - 2010/2/4

Y1 - 2010/2/4

N2 - During their intraerythrocytic development, malaria parasites export hundreds of proteins to remodel their host cell. Nutrient acquisition, cytoadherence and antigenic variation are among the key virulence functions effected by this erythrocyte takeover. Proteins destined for export are synthesized in the endoplasmic reticulum (ER) and cleaved at a conserved (PEXEL) motif, which allows translocation into the host cell via an ATP-driven translocon called the PTEX complex. We report that plasmepsin V, an ER aspartic protease with distant homology to the mammalian processing enzyme BACE, recognizes the PEXEL motif and cleaves it at the correct site. This enzyme is essential for parasite viability and ER residence is essential for its function. We propose that plasmepsin V is the PEXEL protease and is an attractive enzyme for antimalarial drug development. © 2010 Macmillan Publishers Limited. All rights reserved.

AB - During their intraerythrocytic development, malaria parasites export hundreds of proteins to remodel their host cell. Nutrient acquisition, cytoadherence and antigenic variation are among the key virulence functions effected by this erythrocyte takeover. Proteins destined for export are synthesized in the endoplasmic reticulum (ER) and cleaved at a conserved (PEXEL) motif, which allows translocation into the host cell via an ATP-driven translocon called the PTEX complex. We report that plasmepsin V, an ER aspartic protease with distant homology to the mammalian processing enzyme BACE, recognizes the PEXEL motif and cleaves it at the correct site. This enzyme is essential for parasite viability and ER residence is essential for its function. We propose that plasmepsin V is the PEXEL protease and is an attractive enzyme for antimalarial drug development. © 2010 Macmillan Publishers Limited. All rights reserved.

KW - Amino Acid Motifs

KW - Animals

KW - Antimalarials/pharmacology

KW - Aspartic Acid Endopeptidases/antagonists &

KW - inhibitors/chemistry/genetics/metabolism

KW - Biocatalysis/drug effects

KW - Endoplasmic Reticulum/enzymology/metabolism

KW - Erythrocytes/cytology/metabolism/parasitology

KW - Genes, Dominant

KW - Genes, Essential

KW - HIV Protease Inhibitors/pharmacology

KW - Humans

KW - Malaria, Falciparum/blood/metabolism/parasitology/pathology

KW - Multiprotein Complexes/metabolism

KW - Pepstatins/pharmacology

KW - Phenotype

KW - Plasmids/genetics

KW - Plasmodium falciparum/enzymology/genetics/metabolism/pathogenicity

KW - Protein Binding

KW - Protein Sorting Signals

KW - Protein Structure, Tertiary

KW - Protein Transport

KW - Proteomics

KW - Protozoan Proteins/chemistry/metabolism

KW - Substrate Specificity

U2 - 10.1038/nature08726

DO - 10.1038/nature08726

M3 - Article

SN - 0028-0836

VL - 463

SP - 632

EP - 636

JO - Nature

JF - Nature

IS - 7281

ER -

Plasmepsin v licenses Plasmodium proteins for export into the host erythrocyte

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this