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| - | <StructureSection load='' size='450' side='right' scene='underdevelopment' caption=''> | + | <StructureSection load='' size='450' side='right' scene='89/895271/Cv/3' caption=''> |
| | ===Structural insight into DNA recognition by bacterial transcriptional regulators of the SorC/DeoR family=== | | ===Structural insight into DNA recognition by bacterial transcriptional regulators of the SorC/DeoR family=== |
| | <big>Marketa Soltysova, Irena Sieglova, Milan Fabry, Jirı Brynda, Jana Skerlova | | <big>Marketa Soltysova, Irena Sieglova, Milan Fabry, Jirı Brynda, Jana Skerlova |
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| | <hr/> | | <hr/> |
| | <b>Molecular Tour</b><br> | | <b>Molecular Tour</b><br> |
| - | SorC (SorC/DeoR) protein family (Pfam family Sugar-bind: PF04198, (1) ) is one of the large families of bacterial transcriptional regulators, predominantly repressors, that are known for their roles in the regulation of carbohydrate metabolism and quorum-sensing in more than 2,500 bacterial species. For example, among the most studied members are CggR (2-4) or LsrR (5,6). SorC protomers consist of a large C terminal effector binding domain (EBD) and a much smaller N terminal DNA binding domain (DBD). As an assembly, SorC proteins work as tetramers in a cooperative manner, to our best knowledge (4,7). | + | SorC (SorC/DeoR) protein family (Pfam family Sugar-bind: PF04198<ref name="Finn">PMID:18039703</ref>) is one of the large families of bacterial transcriptional regulators, predominantly repressors, that are known for their roles in the regulation of carbohydrate metabolism and quorum-sensing in more than 2,500 bacterial species. For example, among the most studied members are CggR<ref name="Chaix">PMID:20462860</ref>,<ref name="Rezacova">PMID:18554327</ref>,<ref name="Zorilla">PMID:17293407</ref> or LsrR<ref name="Xavier">PMID:15601708</ref>,<ref name="Ha">PMID:24047255</ref>. SorC protomers consist of a large C terminal effector binding domain (EBD) and a much smaller N terminal DNA binding domain (DBD). As an assembly, SorC proteins work as tetramers in a cooperative manner, to our best knowledge<ref name="Zorilla">PMID:17293407</ref>,<ref name="Zeng">PMID:10714997</ref>. |
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| - | So far (2021), several 3D structures of SorC EBDs have been determined. They belong to the so-called NagB-like family for their homology with glucosamine 6 phosphate deaminases from the NagB family, characterized by the central Rossman fold (3,8,9). On the other hand, information on the structure of DNA-binding domains of SorC-family proteins is rather limited. SorC DBDs belong to the most abundant helix turn helix (HTH) superfamily and, by their sequences and structures, they cluster into two subfamilies: SorC/DeoR and SorC/CggR. | + | So far (2021), several 3D structures of SorC EBDs have been determined. They belong to the so-called NagB-like family for their homology with glucosamine 6 phosphate deaminases from the NagB family, characterized by the central Rossman fold<ref name="Rezacova">PMID:18554327</ref>,<ref name="Skerlova">PMID:24863636</ref>,<ref name="Sanctis">PMID:19232357</ref>. On the other hand, information on the structure of DNA-binding domains of SorC-family proteins is rather limited. SorC DBDs belong to the most abundant helix turn helix (HTH) superfamily and, by their sequences and structures, they cluster into two subfamilies: SorC/DeoR and SorC/CggR. |
| - | SorC/DeoR DBD is smaller and consists of the HTH bundle followed by a “β linker†(9), and the bigger SorC/CggR belong to the winged HTH family (10). | + | SorC/DeoR DBD is smaller and consists of the HTH bundle followed by a "β linker"<ref name="Sanctis">PMID:19232357</ref>, and the bigger SorC/CggR belong to the winged HTH family<ref name="Doan">PMID:12622823</ref>. |
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| - | In this paper, we present the first structure of SorC DBDs bound to DNA duplexes. We show DBD structures of representatives of each subfamily, DeoR and CggR, and compare their binding mode, which is likely common to all SorC family members. | + | In this paper, we present the first structure of SorC DBDs bound to DNA duplexes. We show DBD structures of representatives of each subfamily, <scene name='89/895271/Cv/4'>DeoR</scene> and <scene name='89/895271/Cv/7'>CggR</scene>, and compare their binding mode, which is likely common to all SorC family members. |
| | + | *<scene name='89/895271/Cv/4'>A cartoon representation of the bsDeoRDBD dimer bound to the DNA operator</scene>. First monomer is colored in red and the second one is in salmon. |
| | + | *<scene name='89/895271/Cv/7'>A cartoon representation of the bsCggRDBD dimer bound to the DNA operator</scene>. ''bs''CggRDBD comprises five α-helices and two β-strands, with a topology of four α-helices α1 (1–13), α2 (15–32), α3 (37–43) and α4 (48–61) followed by <scene name='89/895271/Cv/8'>a β-hairpin (called a wing) formed by β1 (64–66) and β2 (71–73)</scene> and continuing with a final α-helix (75–89) that links the N-terminal DBD to the C-terminal EBD (α-helices are colored in red, β-strands are in yellow and second monomer is in salmon). |
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| - | References:
| + | *<scene name='89/895271/Cv/15'>Morph showing the conformational change of bsDeoR-DBD upon DNA binding</scene>. DNA-free ''bs''DeoRDBD is colored in pink and DNA-bound ''bs''DeoRDBD is in red. <jmol><jmolButton> |
| - | 1. Finn, R.D., Tate, J., Mistry, J., Coggill, P.C., Sammut, S.J., Hotz, H.R., Ceric, G., Forslund, K., Eddy, S.R., Sonnhammer, E.L. et al. (2008) The Pfam protein families database. Nucleic Acids Res, 36, D281-288.
| + | <script>if (_animating); anim pause;set echo bottom left; color echo white; font echo 20 sansserif;echo Animation Paused; else; anim resume; set echo off;endif;</script> |
| - | 2. Chaix, D., Ferguson, M.L., Atmanene, C., Dorsselaer, A.V., Sanglier-Cianférani, S., Royer, C.A. and Declerck, N. (2010) Physical basis of the inducer-dependent cooperativity of the Central glycolytic genes Repressor/DNA complex. Nucleic Acids Res, 38, 5944-5957.
| + | <text>Stop Animation</text> |
| - | 3. Rezacova, P., Kozisek, M., Moy, S.F., Sieglova, I., Joachimiak, A., Machius, M. and Otwinowski, Z. (2008) Crystal structures of the effector-binding domain of repressor Central glycolytic gene Regulator from Bacillus subtilis reveal ligand-induced structural changes upon binding of several glycolytic intermediates. Molecular Microbiology, 69, 895-910.
| + | </jmolButton></jmol> |
| - | 4. Zorilla, S., Doan, T., Alfonso, C., Margeat, E., Ortega, A., Rivas, G., Aymerich, S., Royer, C.A. and Declerck, N. (2007) Inducer-Modulated Cooperative Binding of the Tetrameric CggR Repressor to Operator DNA. Biohysical Journal, 92, 3215-3227.
| + | |
| - | 5. Xavier, K.B. and Bassler, B.L. (2005) Regulation of uptake and processing of the quorum-sensing autoinducer AI-2 in Escherichia coli. J Bacteriol, 187, 238-248.
| + | '''PDB references:''' DNA-binding domain of DeoR in complex with DNA operator, [[7bhy]]; DNA-binding domain of CggR in complex with DNA operator, [[7oyk]]. |
| - | 6. Ha, J.H., Eo, Y., Grishaev, A., Guo, M., Smith, J.A., Sintim, H.O., Kim, E.H., Cheong, H.K., Bentley, W.E. and Ryu, K.S. (2013) Crystal structures of the LsrR proteins complexed with phospho-AI-2 and two signal-interrupting analogues reveal distinct mechanisms for ligand recognition. J Am Chem Soc, 135, 15526-15535.
| + | |
| - | 7. Zeng, X., Saxild, H.H. and Switzer, R.L. (2000) Purification and Characterization of the DeoR Repressor of Bacillus subtilis. Journal of Bacteriology, 182, 1916-1922.
| + | |
| - | 8. Skerlova, J., Fabry, M., Hubalek, M., Otwinowski, Z. and Rezacova, P. (2014) Structure of the effectorâ€binding domain of deoxyribonucleoside regulator DeoR from Bacillus subtilis. The FEBS Journal, 281, 4280-4292.
| + | |
| - | 9. de Sanctis, D., McVey, C.E., Enguita, F.J. and Carrondo, M.A. (2009) Crystal structure of the full-length sorbitol operon regulator SorC from Klebsiella pneumoniae: structural evidence for a novel transcriptional regulation mechanism. J Mol Biol, 387, 759-770.
| + | |
| - | 10. Doan, T. and Aymerich, S. (2003) Regulation of the central glycolytic genes in Bacillus subtilis: binding of the repressor CggR to its single DNA target sequence is modulated by fructose-1,6-bisphosphate. Mol Microbiol, 47, 1709-1721.
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| | <b>References</b><br> | | <b>References</b><br> |
| Structural insight into DNA recognition by bacterial transcriptional regulators of the SorC/DeoR family
Marketa Soltysova, Irena Sieglova, Milan Fabry, Jirı Brynda, Jana Skerlova
and Pavlına Rezacova [1]
Molecular Tour
SorC (SorC/DeoR) protein family (Pfam family Sugar-bind: PF04198[2]) is one of the large families of bacterial transcriptional regulators, predominantly repressors, that are known for their roles in the regulation of carbohydrate metabolism and quorum-sensing in more than 2,500 bacterial species. For example, among the most studied members are CggR[3],[4],[5] or LsrR[6],[7]. SorC protomers consist of a large C terminal effector binding domain (EBD) and a much smaller N terminal DNA binding domain (DBD). As an assembly, SorC proteins work as tetramers in a cooperative manner, to our best knowledge[5],[8].
So far (2021), several 3D structures of SorC EBDs have been determined. They belong to the so-called NagB-like family for their homology with glucosamine 6 phosphate deaminases from the NagB family, characterized by the central Rossman fold[4],[9],[10]. On the other hand, information on the structure of DNA-binding domains of SorC-family proteins is rather limited. SorC DBDs belong to the most abundant helix turn helix (HTH) superfamily and, by their sequences and structures, they cluster into two subfamilies: SorC/DeoR and SorC/CggR.
SorC/DeoR DBD is smaller and consists of the HTH bundle followed by a "β linker"[10], and the bigger SorC/CggR belong to the winged HTH family[11].
In this paper, we present the first structure of SorC DBDs bound to DNA duplexes. We show DBD structures of representatives of each subfamily, and , and compare their binding mode, which is likely common to all SorC family members.
- . First monomer is colored in red and the second one is in salmon.
- . bsCggRDBD comprises five α-helices and two β-strands, with a topology of four α-helices α1 (1–13), α2 (15–32), α3 (37–43) and α4 (48–61) followed by and continuing with a final α-helix (75–89) that links the N-terminal DBD to the C-terminal EBD (α-helices are colored in red, β-strands are in yellow and second monomer is in salmon).
- . DNA-free bsDeoRDBD is colored in pink and DNA-bound bsDeoRDBD is in red.
PDB references: DNA-binding domain of DeoR in complex with DNA operator, 7bhy; DNA-binding domain of CggR in complex with DNA operator, 7oyk.
References
- ↑ Soltysova M, Sieglova I, Fabry M, Brynda J, Skerlova J, Rezacova P. Structural insight into DNA recognition by bacterial transcriptional regulators of the SorC/DeoR family. Acta Crystallogr D Struct Biol. 2021 Nov 1;77(Pt 11):1411-1424. doi:, 10.1107/S2059798321009633. Epub 2021 Oct 20. PMID:34726169 doi:http://dx.doi.org/10.1107/S2059798321009633
- ↑ Finn RD, Tate J, Mistry J, Coggill PC, Sammut SJ, Hotz HR, Ceric G, Forslund K, Eddy SR, Sonnhammer EL, Bateman A. The Pfam protein families database. Nucleic Acids Res. 2008 Jan;36(Database issue):D281-8. doi: 10.1093/nar/gkm960., Epub 2007 Nov 26. PMID:18039703 doi:http://dx.doi.org/10.1093/nar/gkm960
- ↑ Chaix D, Ferguson ML, Atmanene C, Van Dorsselaer A, Sanglier-Cianferani S, Royer CA, Declerck N. Physical basis of the inducer-dependent cooperativity of the Central glycolytic genes Repressor/DNA complex. Nucleic Acids Res. 2010 Sep;38(17):5944-57. doi: 10.1093/nar/gkq334. Epub 2010, May 12. PMID:20462860 doi:http://dx.doi.org/10.1093/nar/gkq334
- ↑ 4.0 4.1 Rezacova P, Kozisek M, Moy SF, Sieglova I, Joachimiak A, Machius M, Otwinowski Z. Crystal structures of the effector-binding domain of repressor CggR from Bacillus subtilis reveal ligand-induced structural changes upon binding of several glycolytic intermediates. Mol Microbiol. 2008 Jun 10;. PMID:18554327 doi:MMI6318
- ↑ 5.0 5.1 Zorrilla S, Doan T, Alfonso C, Margeat E, Ortega A, Rivas G, Aymerich S, Royer CA, Declerck N. Inducer-modulated cooperative binding of the tetrameric CggR repressor to operator DNA. Biophys J. 2007 May 1;92(9):3215-27. doi: 10.1529/biophysj.106.095109. Epub 2007 , Feb 9. PMID:17293407 doi:http://dx.doi.org/10.1529/biophysj.106.095109
- ↑ Xavier KB, Bassler BL. Regulation of uptake and processing of the quorum-sensing autoinducer AI-2 in Escherichia coli. J Bacteriol. 2005 Jan;187(1):238-48. PMID:15601708 doi:http://dx.doi.org/187/1/238
- ↑ Ha JH, Eo Y, Grishaev A, Guo M, Smith JA, Sintim HO, Kim EH, Cheong HK, Bentley WE, Ryu KS. Crystal Structures of the LsrR Proteins Complexed with Phospho-AI-2 and Two Signal-Interrupting Analogues Reveal Distinct Mechanisms for Ligand Recognition. J Am Chem Soc. 2013 Oct 16;135(41):15526-35. doi: 10.1021/ja407068v. Epub 2013, Oct 1. PMID:24047255 doi:http://dx.doi.org/10.1021/ja407068v
- ↑ Zeng X, Saxild HH, Switzer RL. Purification and characterization of the DeoR repressor of Bacillus subtilis. J Bacteriol. 2000 Apr;182(7):1916-22. doi: 10.1128/JB.182.7.1916-1922.2000. PMID:10714997 doi:http://dx.doi.org/10.1128/JB.182.7.1916-1922.2000
- ↑ Skerlova J, Fabry M, Hubalek M, Otwinowski Z, Rezacova P. Structure of the effector-binding domain of deoxyribonucleoside regulator DeoR from Bacillus subtilis. FEBS J. 2014 May 23. doi: 10.1111/febs.12856. PMID:24863636 doi:http://dx.doi.org/10.1111/febs.12856
- ↑ 10.0 10.1 de Sanctis D, McVey CE, Enguita FJ, Carrondo MA. Crystal structure of the full-length sorbitol operon regulator SorC from Klebsiella pneumoniae: structural evidence for a novel transcriptional regulation mechanism. J Mol Biol. 2009 Apr 3;387(3):759-70. Epub 2009 Feb 14. PMID:19232357 doi:10.1016/j.jmb.2009.02.017
- ↑ Doan T, Aymerich S. Regulation of the central glycolytic genes in Bacillus subtilis: binding of the repressor CggR to its single DNA target sequence is modulated by fructose-1,6-bisphosphate. Mol Microbiol. 2003 Mar;47(6):1709-21. PMID:12622823
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