Hemoglobin receptor in Leishmania is a hexokinase located in the flagellar pocket
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Hb endocytosis in Leishmania is mediated through a 46-kDa protein located in the flagellar pocket. To understand the nature of the Hb receptor (HbR), we have purified the 46-kDa protein to homogeneity from Leishmania promastigote membrane. Purified HbR specifically binds Hb. The gene for HbR was cloned, and sequence analysis of the full-length HbR gene indicates the presence of hexokinase (HK) signature sequences, ATP-binding domain, and PTS-II motif. Four lines of evidence indicate that HbR in Leishmania is a hexokinase: 1) the recombinant HbR binds Hb, and the Hb-binding domain resides in the N terminus of the protein; 2) recombinant proteins and cell lysate prepared from HbR-overexpressing Leishmania promastigotes show enhanced HK activity in comparison with untransfected cells; 3) immunolocalization studies using antibodies against the N-terminal fragment (Ld-HbR-DeltaC) of Ld-HbR indicate that this protein is located in the flagellar pocket of Leishmania; and 4) binding and uptake of (125)I-Hb by Leishmania is significantly inhibited by anti-Ld-HbR-DeltaC antibody and Ld-HbR-DeltaC, respectively. Taken together, these results indicate that HK present in the flagellar pocket of Leishmania is involved in Hb endocytosis.
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Leishmania species are unable to synthesize heme by themselves and express receptors for the uptake of HB or heme.
“In contrast to P. falciparum, Leishmania species, which can cause skin, mucocutaneous or systemic infections, are unable to synthesize heme by themselves and thus express receptors for the uptake of HB or heme, respectively (Krishnamurthy et al., 2005;Patel et al., 2008).”
From Iron in infection and immunity (2020) · cites this paper as Krishnamurthy et al., 2005
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- Authors
- Krishnamurthy, G., Vikram, R., Singh, S. B., Patel, N., Agarwal, S., Mukhopadhyay, G., Basu, S. K., & Mukhopadhyay, A.
- Affiliations
- National Institute of Immunology (IN)
- Jawaharlal Nehru University (IN)
- Corresponding author
- Mukhopadhyay, Amitabha
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-02
- Volume
- 280
- Issue
- 7
- Pages
- 5884-5891
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2146183220
- Cited by
- 83
- References
- 40
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 5 · 2022: 3 · 2021: 2 · 2020: 8 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 9 · 2015: 3 · 2014: 5 · 2013: 5 · 2012: 4
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
- Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
- Health Sciences › Medicine › Pharmacology › Leech Biology and Applications
- Keywords
- hemoglobin receptor, Leishmania, hexokinase, flagellar pocket, hemoglobin uptake, promastigotes, hemoglobin binding, protein purification, gene cloning
- MeSH terms
- Adenosine Triphosphate, Amino Acid Sequence, Animals, Cloning, Molecular, Flagella, Hemoglobins, Hexokinase, Kinetics, Leishmania donovani, Molecular Sequence Data, Molecular Weight, Protein Binding, Recombinant Proteins, Substrate Specificity, Protozoan Proteins, Protein Structure, Tertiary
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