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A De novo Peptide from a High Throughput Peptide Library Blocks Myosin A -MTIP Complex Formation in Plasmodium falciparum .
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2020 Aug 26; Vol. 21 (17). Date of Electronic Publication: 2020 Aug 26. - Publication Year :
- 2020
-
Abstract
- Apicomplexan parasites, through their motor machinery, produce the required propulsive force critical for host cell-entry. The conserved components of this so-called glideosome machinery are myosin A and myosin A Tail Interacting Protein (MTIP). MTIP tethers myosin A to the inner membrane complex of the parasite through 20 amino acid-long C-terminal end of myosin A that makes direct contacts with MTIP, allowing the invasion of Plasmodium falciparum in erythrocytes. Here, we discovered through screening a peptide library, a de-novo peptide ZA1 that binds the myosin A tail domain. We demonstrated that ZA1 bound strongly to myosin A tail and was able to disrupt the native myosin A tail MTIP complex both in vitro and in vivo. We then showed that a shortened peptide derived from ZA1, named ZA1S, was able to bind myosin A and block parasite invasion. Overall, our study identified a novel anti-malarial peptide that could be used in combination with other antimalarials for blocking the invasion of Plasmodium falciparum .
- Subjects :
- Amino Acid Motifs
Antimalarials chemistry
Binding Sites
Drug Evaluation, Preclinical
Erythrocytes parasitology
High-Throughput Screening Assays
Humans
Membrane Proteins chemistry
Models, Molecular
Multiprotein Complexes drug effects
Nonmuscle Myosin Type IIA chemistry
Peptide Library
Peptides chemistry
Plasmodium falciparum drug effects
Plasmodium falciparum metabolism
Protein Binding
Protozoan Proteins chemistry
Protozoan Proteins metabolism
Antimalarials pharmacology
Membrane Proteins metabolism
Nonmuscle Myosin Type IIA metabolism
Peptides pharmacology
Plasmodium falciparum growth & development
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 21
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 32859024
- Full Text :
- https://doi.org/10.3390/ijms21176158