Abstract
Leishmania internalize hemoglobin (Hb) via a specific receptor (HbR) for their survival. To identify the Hb-binding domain of HbR, we cloned and expressed several truncated proteins of HbR and determined their ability to bind Hb. Our findings reveal that 90% of Hb-binding activity is retained in HbR41-80 in comparison with HbR1-471 . We synthesized a 40 amino acid peptide (SSEKMKQLTMYMIHEMVEGLEGRPSTVRMLPSFVYTSDPA) corresponding to HbR41-80 and found that it specifically binds Hb. Subsequently, we found that the HbR41-80 peptide completely blocks Hb uptake in both promastigote and amastigote forms of Leishmania and, thereby, inhibits the growth of the parasite. These results demonstrate that HbR41-80 is the Hb-binding domain of HbR, which might be used as a potential therapeutic agent to inhibit the growth of Leishmania.
Keywords:
Leishmania; domain; endocytosis; hemoglobin; receptor.
© 2020 Federation of European Biochemical Societies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Antiprotozoal Agents / chemical synthesis
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Antiprotozoal Agents / metabolism*
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Antiprotozoal Agents / pharmacology
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Binding, Competitive
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Cloning, Molecular
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Escherichia coli / genetics
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Escherichia coli / metabolism
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Gene Expression
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Genetic Vectors / chemistry
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Genetic Vectors / metabolism
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Hemoglobins / chemistry*
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Hemoglobins / metabolism
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Leishmania donovani / drug effects
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Leishmania donovani / genetics
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Leishmania donovani / growth & development
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Leishmania donovani / metabolism*
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Life Cycle Stages / drug effects
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Life Cycle Stages / genetics*
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Models, Molecular
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Peptides / chemical synthesis
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Peptides / metabolism*
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Peptides / pharmacology
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Protein Binding
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Protein Conformation, alpha-Helical
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Protein Conformation, beta-Strand
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Protein Interaction Domains and Motifs
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Protozoan Proteins / chemistry*
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Protozoan Proteins / genetics
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Protozoan Proteins / metabolism
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Receptors, Cell Surface / chemistry*
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Structural Homology, Protein
Substances
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Antiprotozoal Agents
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Hemoglobins
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Peptides
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Protozoan Proteins
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Receptors, Cell Surface
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Recombinant Proteins