User:Anielle Salviano de Almeida Ferrari/Sandbox 1
From Proteopedia
| Line 4: | Line 4: | ||
The [https://en.wikipedia.org/wiki/Leptospirosis leptospirosis] is caused by [https://en.wikipedia.org/wiki/Spirochaete spirochaetes] of pathogenic species of genus [https://en.wikipedia.org/wiki/Leptospira ''Leptospira''] and is a emerging zoonotic disease worldwide <ref name="nimbus1">DOI 10.1016/j.jmb.2017.06.002</ref> <ref name="nimbus2">DOI 10.1371/journal.pntd.0007270</ref>.According to the [https://www.who.int/ World Health Organization (WHO)], approximately 1 million people become infected with leptospiras per year and 60,000 die from the disease worldwide <ref name="nimbus3">DOI 10.1371/journal.pntd.0003898</ref>.The ability of some ''Leptospira'' species to grow in different conditions, such as in soil, water and in different mammalian organs and in the bloodstream, suggests that the bacteria must have different signaling pathways to detect the external environment and modulate its gene expression. One way to respond to environmental changes and modulate gene expression is through the production of bis (3 ′, 5 ′) - cyclic diguanylic acid, known as [https://en.wikipedia.org/wiki/Cyclic_di-GMP cyclic di-GMP (c-di-GMP) ] <ref name="nimbus1"/>. However, to date, almost nothing is known about c-di-GMP signaling in ''Leptospira''<ref name="nimbus1"/> <ref name="nimbus4">DOI 10.3389/fmicb.2018.00764</ref><ref name="nimbus5">DOI 10.1038/s41522-020-0134-1</ref><ref name="nimbus6">DOI 10.1038/s41467-021-22492-7 </ref>. | The [https://en.wikipedia.org/wiki/Leptospirosis leptospirosis] is caused by [https://en.wikipedia.org/wiki/Spirochaete spirochaetes] of pathogenic species of genus [https://en.wikipedia.org/wiki/Leptospira ''Leptospira''] and is a emerging zoonotic disease worldwide <ref name="nimbus1">DOI 10.1016/j.jmb.2017.06.002</ref> <ref name="nimbus2">DOI 10.1371/journal.pntd.0007270</ref>.According to the [https://www.who.int/ World Health Organization (WHO)], approximately 1 million people become infected with leptospiras per year and 60,000 die from the disease worldwide <ref name="nimbus3">DOI 10.1371/journal.pntd.0003898</ref>.The ability of some ''Leptospira'' species to grow in different conditions, such as in soil, water and in different mammalian organs and in the bloodstream, suggests that the bacteria must have different signaling pathways to detect the external environment and modulate its gene expression. One way to respond to environmental changes and modulate gene expression is through the production of bis (3 ′, 5 ′) - cyclic diguanylic acid, known as [https://en.wikipedia.org/wiki/Cyclic_di-GMP cyclic di-GMP (c-di-GMP) ] <ref name="nimbus1"/>. However, to date, almost nothing is known about c-di-GMP signaling in ''Leptospira''<ref name="nimbus1"/> <ref name="nimbus4">DOI 10.3389/fmicb.2018.00764</ref><ref name="nimbus5">DOI 10.1038/s41522-020-0134-1</ref><ref name="nimbus6">DOI 10.1038/s41467-021-22492-7 </ref>. | ||
| + | |||
| + | == Function == | ||
| + | <scene name='89/898355/Assymetric_unit/3'>Lcd1</scene> is coded by the ''LIC_13137'' encoded a diguanylate cyclases that produced c-di-GMP in ''L. interrogans'' serovar Copenhageni strain Fiocruz L1-130. Lcd1 has two domains: the N-terminal GAF domain (residues 26-165) and the C-terminal GGDEF domain (residues 178-326) with a linker between them (residues 166-177)<ref name="nimbus1"/>. | ||
| + | C-di-GMP is responsible for several behaviors in bacteria, such as [https://en.wikipedia.org/wiki/Biofilm biofilm], cell cycle, motility, chemotaxis, [https://en.wikipedia.org/wiki/Quorum_sensing quorum sensing], virulence, and may the action of regular [https://en.wikipedia.org/wiki/Riboswitch riboswitches] <ref name="nimbus7">DOI 10.1128/MMBR.00043-12</ref>. Despite the efforts of different mechanisms of the immune system to eliminate infection by leptospires, these bacteria are able to evade the immune system and survive. A possible evasion mechanism is the production of biofilms, which helps bacteria to organize a physical-chemical barrier against the immune system and against antimicrobial agents <ref name="nimbus8">PMID: 23102459</ref>. | ||
| + | |||
| + | The gene ''LIC13137'' has orthologs only in pathogenic species of ''Leptospira'', with >23% identity. But, ''LIC13137'' has only paralog, ''LIC12273'', with the same architecture domain (GAF-GGDEF domain), founded in pathogenic and non-pathogenic species of ''Leptospira''. Therefore, an elucidation of the production of Lcd1 by ''L. interrogans'' helps to understand the bacteria's virulence. | ||
| + | |||
| + | [[Image:Filogenia.jpg|800px|center|]] | ||
| + | |||
== Structure of Lcd1 == | == Structure of Lcd1 == | ||
| - | Lcd1 has two domains: the N-terminal GAF domain (residues 26-165) and the C-terminal GGDEF domain (residues 178-326) with a linker between them (residues 166-177)<ref name="nimbus1"/>. | ||
The fragment contained the [https://en.wikipedia.org/wiki/GAF_domain GAF domain] (residues 1 – 180) was purified and used in the thermal denaturation experiments in the presence of various cyclic nucleotides. In the addition of [https://en.wikipedia.org/wiki/Cyclic_adenosine_monophosphate 3′,5′-cyclic adenosine monophosphate] increases the thermal stability, despites the other ligands tested 3′,5′-cyclic guanosine monophosphate [https://en.wikipedia.org/wiki/Cyclic_guanosine_monophosphate (cGMP)] and c-di-GMP do not alter significantly <ref name="nimbus1"/>. | The fragment contained the [https://en.wikipedia.org/wiki/GAF_domain GAF domain] (residues 1 – 180) was purified and used in the thermal denaturation experiments in the presence of various cyclic nucleotides. In the addition of [https://en.wikipedia.org/wiki/Cyclic_adenosine_monophosphate 3′,5′-cyclic adenosine monophosphate] increases the thermal stability, despites the other ligands tested 3′,5′-cyclic guanosine monophosphate [https://en.wikipedia.org/wiki/Cyclic_guanosine_monophosphate (cGMP)] and c-di-GMP do not alter significantly <ref name="nimbus1"/>. | ||
| Line 13: | Line 21: | ||
The structure of the Lcd1-GAF <scene name='89/898355/Monomer/3'>monomer</scene> is composed by three-helix bundle (α1 - α2 – α3), six antiparallel strands (β3 – β2 – β1 – β6 – β5 – β4), and more four α-helices, three small (α4 – α5 – α6) and a one 310 helix (α310). The domain GAF is divided by two <scene name='89/898355/Monomer_subdomains/1'>subdomains</scene>: the dimerization domain (DD) in and the ligand binding subdomain (BD). | The structure of the Lcd1-GAF <scene name='89/898355/Monomer/3'>monomer</scene> is composed by three-helix bundle (α1 - α2 – α3), six antiparallel strands (β3 – β2 – β1 – β6 – β5 – β4), and more four α-helices, three small (α4 – α5 – α6) and a one 310 helix (α310). The domain GAF is divided by two <scene name='89/898355/Monomer_subdomains/1'>subdomains</scene>: the dimerization domain (DD) in and the ligand binding subdomain (BD). | ||
| - | == Function == | ||
| - | <scene name='89/898355/Assymetric_unit/3'>Lcd1</scene> is coded by the ''LIC_13137'' encoded a diguanylate cyclases that produced c-di-GMP in ''L. interrogans'' serovar Copenhageni strain Fiocruz L1-130. C-di-GMP is responsible for several behaviors in bacteria, such as [https://en.wikipedia.org/wiki/Biofilm biofilm], cell cycle, motility, chemotaxis, [https://en.wikipedia.org/wiki/Quorum_sensing quorum sensing], virulence, and may the action of regular [https://en.wikipedia.org/wiki/Riboswitch riboswitches] <ref name="nimbus7">DOI 10.1128/MMBR.00043-12</ref>. Despite the efforts of different mechanisms of the immune system to eliminate infection by leptospires, these bacteria are able to evade the immune system and survive. A possible evasion mechanism is the production of biofilms, which helps bacteria to organize a physical-chemical barrier against the immune system and against antimicrobial agents <ref name="nimbus8">PMID: 23102459</ref>. | ||
| - | |||
| - | The gene "LIC13137" has orthologs only in pathogenic species of "Leptospira", with >23% identity. But, "LIC13137" has only paralog, "LIC12273", with the same architecture domain (GAF-GGDEF domain), founded in pathogenic and non-pathogenic species of "Leptospira". Therefore, an elucidation of the production of Lcd1 by ''L. interrogans'' helps to understand the bacteria's virulence. | ||
| - | |||
| - | [[Image:Filogenia.jpg|800px|center|]] | ||
Revision as of 03:32, 13 December 2021
Contents |
Leptospira cAMP-dependent DGC 1 (Lcd1)
|
The leptospirosis is caused by spirochaetes of pathogenic species of genus Leptospira and is a emerging zoonotic disease worldwide [1] [2].According to the World Health Organization (WHO), approximately 1 million people become infected with leptospiras per year and 60,000 die from the disease worldwide [3].The ability of some Leptospira species to grow in different conditions, such as in soil, water and in different mammalian organs and in the bloodstream, suggests that the bacteria must have different signaling pathways to detect the external environment and modulate its gene expression. One way to respond to environmental changes and modulate gene expression is through the production of bis (3 ′, 5 ′) - cyclic diguanylic acid, known as cyclic di-GMP (c-di-GMP) [1]. However, to date, almost nothing is known about c-di-GMP signaling in Leptospira[1] [4][5][6].
Function
is coded by the LIC_13137 encoded a diguanylate cyclases that produced c-di-GMP in L. interrogans serovar Copenhageni strain Fiocruz L1-130. Lcd1 has two domains: the N-terminal GAF domain (residues 26-165) and the C-terminal GGDEF domain (residues 178-326) with a linker between them (residues 166-177)[1]. C-di-GMP is responsible for several behaviors in bacteria, such as biofilm, cell cycle, motility, chemotaxis, quorum sensing, virulence, and may the action of regular riboswitches [7]. Despite the efforts of different mechanisms of the immune system to eliminate infection by leptospires, these bacteria are able to evade the immune system and survive. A possible evasion mechanism is the production of biofilms, which helps bacteria to organize a physical-chemical barrier against the immune system and against antimicrobial agents [8].
The gene LIC13137 has orthologs only in pathogenic species of Leptospira, with >23% identity. But, LIC13137 has only paralog, LIC12273, with the same architecture domain (GAF-GGDEF domain), founded in pathogenic and non-pathogenic species of Leptospira. Therefore, an elucidation of the production of Lcd1 by L. interrogans helps to understand the bacteria's virulence.
Structure of Lcd1
The fragment contained the GAF domain (residues 1 – 180) was purified and used in the thermal denaturation experiments in the presence of various cyclic nucleotides. In the addition of 3′,5′-cyclic adenosine monophosphate increases the thermal stability, despites the other ligands tested 3′,5′-cyclic guanosine monophosphate (cGMP) and c-di-GMP do not alter significantly [1].
The structure deposited in PDB bank was was obtained by crystallizing the GAF domain (residues 1 – 175), called Lcd1-GAF. In the assymetric unit, there are four Lcd1-GAF molecules. But using PISA algoritm for analysis to protein-protein interaction and size-exclusion chromatography (SEC) analysis of apo and holo state of Lcd1-GAF reveals that Lcd1 exists has a . The structure of the Lcd1-GAF is composed by three-helix bundle (α1 - α2 – α3), six antiparallel strands (β3 – β2 – β1 – β6 – β5 – β4), and more four α-helices, three small (α4 – α5 – α6) and a one 310 helix (α310). The domain GAF is divided by two : the dimerization domain (DD) in and the ligand binding subdomain (BD).
References
- ↑ 1.0 1.1 1.2 1.3 1.4 da Costa Vasconcelos FN, Maciel NK, Favaro DC, de Oliveira LC, Barbosa AS, Salinas RK, de Souza RF, Farah CS, Guzzo CR. Structural and Enzymatic Characterization of a cAMP-Dependent Diguanylate Cyclase from Pathogenic Leptospira Species. J Mol Biol. 2017 Jul 21;429(15):2337-2352. doi: 10.1016/j.jmb.2017.06.002. Epub, 2017 Jun 7. PMID:28601495 doi:http://dx.doi.org/10.1016/j.jmb.2017.06.002
- ↑ Vincent AT, Schiettekatte O, Goarant C, Neela VK, Bernet E, Thibeaux R, Ismail N, Mohd Khalid MKN, Amran F, Masuzawa T, Nakao R, Amara Korba A, Bourhy P, Veyrier FJ, Picardeau M. Revisiting the taxonomy and evolution of pathogenicity of the genus Leptospira through the prism of genomics. PLoS Negl Trop Dis. 2019 May 23;13(5):e0007270. doi:, 10.1371/journal.pntd.0007270. eCollection 2019 May. PMID:31120895 doi:http://dx.doi.org/10.1371/journal.pntd.0007270
- ↑ Costa F, Hagan JE, Calcagno J, Kane M, Torgerson P, Martinez-Silveira MS, Stein C, Abela-Ridder B, Ko AI. Global Morbidity and Mortality of Leptospirosis: A Systematic Review. PLoS Negl Trop Dis. 2015 Sep 17;9(9):e0003898. doi: 10.1371/journal.pntd.0003898., eCollection 2015. PMID:26379143 doi:http://dx.doi.org/10.1371/journal.pntd.0003898
- ↑ Xiao G, Kong L, Che R, Yi Y, Zhang Q, Yan J, Lin X. Identification and Characterization of c-di-GMP Metabolic Enzymes of Leptospira interrogans and c-di-GMP Fluctuations After Thermal Shift and Infection. Front Microbiol. 2018 Apr 20;9:764. doi: 10.3389/fmicb.2018.00764. eCollection, 2018. PMID:29755425 doi:http://dx.doi.org/10.3389/fmicb.2018.00764
- ↑ Thibeaux R, Soupe-Gilbert ME, Kainiu M, Girault D, Bierque E, Fernandes J, Bahre H, Douyere A, Eskenazi N, Vinh J, Picardeau M, Goarant C. The zoonotic pathogen Leptospira interrogans mitigates environmental stress through cyclic-di-GMP-controlled biofilm production. NPJ Biofilms Microbiomes. 2020 Jun 12;6(1):24. doi: 10.1038/s41522-020-0134-1. PMID:32532998 doi:http://dx.doi.org/10.1038/s41522-020-0134-1
- ↑ Teixeira RD, Holzschuh F, Schirmer T. Activation mechanism of a small prototypic Rec-GGDEF diguanylate cyclase. Nat Commun. 2021 Apr 12;12(1):2162. doi: 10.1038/s41467-021-22492-7. PMID:33846343 doi:http://dx.doi.org/10.1038/s41467-021-22492-7
- ↑ Romling U, Galperin MY, Gomelsky M. Cyclic di-GMP: the first 25 years of a universal bacterial second messenger. Microbiol Mol Biol Rev. 2013 Mar;77(1):1-52. doi: 10.1128/MMBR.00043-12. PMID:23471616 doi:http://dx.doi.org/10.1128/MMBR.00043-12
- ↑ Brihuega B, Samartino L, Auteri C, Venzano A, Caimi K. In vivo cell aggregations of a recent swine biofilm-forming isolate of Leptospira interrogans strain from Argentina. Rev Argent Microbiol. 2012 Jul-Sep;44(3):138-43. PMID:23102459
