Interaction mechanism of Mycobacterium tuberculosis GroEL2 protein with macrophage Lectin-like, oxidized low-density lipoprotein receptor-1 : An integrated computational and experimental study
Copyright © 2020 Elsevier B.V. All rights reserved..
BACKGROUND: Bacterial surface proteins act as potential adhesins or invasins. The GroEL is a signal peptide-free surface expressed protein that aids adhesion in Escherichia coli by binding to LOX-1 receptor of the host cells. Mycobacterium tuberculosis (Mtb) expresses GroEL2 protein, having high level sequence identity with E. coli GroEL. This study investigates the interaction mechanism of GroEL2 protein of Mtb with LOX-1 of macrophages using integrated computational and experimental approach.
METHODS: Mtb GroEL2 protein was purified as histidine tagged protein using Ni-NTA chromatography. Confocal and scanning electron microscopies were used to study the uptake of GroEL2 coated fluorescent latex beads through the LOX-1 receptor in RAW264.7 macrophage cell line. Docking studies were performed to understand the interaction between the GroEL2 and LOX-1 proteins. Polyinosinic acid (PIA) was used as a LOX-1 inhibitor in both in silico and in vitro experiments.
RESULTS: GroEL2 protein coating enhances uptake of latex beads into macrophages through LOX-1 receptor. LOX-1 inhibitor PIA decreased the uptake of GroEL2 coated latex beads. GroEL2 interacts with the key ligand binding regions of the LOX-1 receptor, such as the basic spine and the saddle hydrophobic patch. PIA molecule destabilized the LOX-1-GroEL2 docked complex.
CONCLUSION: Surface associated GroEL2 protein of Mtb is a potential ligand for macrophage LOX-1 receptor. Interaction between GroEL2 and LOX-1 receptor may be utilized by Mtb to gain its intracellular access.
GENERAL SIGNIFICANCE: Surface associated GroEL2 of Mtb may bind to the macrophage LOX-1 receptor, enabling the internalization of the bacteria and progression of the infection.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2021 |
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Erschienen: |
2021 |
Enthalten in: |
Zur Gesamtaufnahme - volume:1865 |
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Enthalten in: |
Biochimica et biophysica acta. General subjects - 1865(2021), 1 vom: 01. Jan., Seite 129758 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Vinod, Vivek [VerfasserIn] |
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Links: |
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Themen: |
Chaperonin 60 |
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Anmerkungen: |
Date Completed 11.01.2021 Date Revised 11.01.2021 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.bbagen.2020.129758 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM316019429 |
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500 | |a published: Print-Electronic | ||
500 | |a Citation Status MEDLINE | ||
520 | |a Copyright © 2020 Elsevier B.V. All rights reserved. | ||
520 | |a BACKGROUND: Bacterial surface proteins act as potential adhesins or invasins. The GroEL is a signal peptide-free surface expressed protein that aids adhesion in Escherichia coli by binding to LOX-1 receptor of the host cells. Mycobacterium tuberculosis (Mtb) expresses GroEL2 protein, having high level sequence identity with E. coli GroEL. This study investigates the interaction mechanism of GroEL2 protein of Mtb with LOX-1 of macrophages using integrated computational and experimental approach | ||
520 | |a METHODS: Mtb GroEL2 protein was purified as histidine tagged protein using Ni-NTA chromatography. Confocal and scanning electron microscopies were used to study the uptake of GroEL2 coated fluorescent latex beads through the LOX-1 receptor in RAW264.7 macrophage cell line. Docking studies were performed to understand the interaction between the GroEL2 and LOX-1 proteins. Polyinosinic acid (PIA) was used as a LOX-1 inhibitor in both in silico and in vitro experiments | ||
520 | |a RESULTS: GroEL2 protein coating enhances uptake of latex beads into macrophages through LOX-1 receptor. LOX-1 inhibitor PIA decreased the uptake of GroEL2 coated latex beads. GroEL2 interacts with the key ligand binding regions of the LOX-1 receptor, such as the basic spine and the saddle hydrophobic patch. PIA molecule destabilized the LOX-1-GroEL2 docked complex | ||
520 | |a CONCLUSION: Surface associated GroEL2 protein of Mtb is a potential ligand for macrophage LOX-1 receptor. Interaction between GroEL2 and LOX-1 receptor may be utilized by Mtb to gain its intracellular access | ||
520 | |a GENERAL SIGNIFICANCE: Surface associated GroEL2 of Mtb may bind to the macrophage LOX-1 receptor, enabling the internalization of the bacteria and progression of the infection | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a GroEL2 | |
650 | 4 | |a LOX-1 | |
650 | 4 | |a M. tuberculosis | |
650 | 4 | |a Macrophage uptake | |
650 | 4 | |a Molecular docking | |
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700 | 1 | |a Kumar, Anil |e verfasserin |4 aut | |
700 | 1 | |a Mohan, Chethampadi Gopi |e verfasserin |4 aut | |
700 | 1 | |a Biswas, Raja |e verfasserin |4 aut | |
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