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Structural basis for the toxic activity of MafB2 from maf genomic island 2 (MGI-2) in N. meningitidis B16B6

The Maf polymorphic toxin system is involved in conflict between strains found in pathogenic Neisseria species such as Neisseria meningitidis and Neisseria gonorrhoeae. The genes encoding the Maf polymorphic toxin system are found in specific genomic islands called maf genomic islands (MGIs). In the...

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Autores principales: Park, So Hyeon, Jeong, Sun Ju, Ha, Sung Chul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9970974/
https://www.ncbi.nlm.nih.gov/pubmed/36849501
http://dx.doi.org/10.1038/s41598-023-30528-9
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author Park, So Hyeon
Jeong, Sun Ju
Ha, Sung Chul
author_facet Park, So Hyeon
Jeong, Sun Ju
Ha, Sung Chul
author_sort Park, So Hyeon
collection PubMed
description The Maf polymorphic toxin system is involved in conflict between strains found in pathogenic Neisseria species such as Neisseria meningitidis and Neisseria gonorrhoeae. The genes encoding the Maf polymorphic toxin system are found in specific genomic islands called maf genomic islands (MGIs). In the MGIs, the MafB and MafI encode toxin and immunity proteins, respectively. Although the C-terminal region of MafB (MafB-CT) is specific for toxic activity, the underlying enzymatic activity that renders MafB-CT toxic is unknown in many MafB proteins due to lack of homology with domain of known function. Here we present the crystal structure of the MafB2-CT(MGI-2B16B6)/MafI2(MGI-2B16B6) complex from N. meningitidis B16B6. MafB2-CT(MGI-2B16B6) displays an RNase A fold similar to mouse RNase 1, although the sequence identity is only ~ 14.0%. MafB2-CT(MGI-2B16B6) forms a 1:1 complex with MafI2(MGI-2B16B6) with a Kd value of ~ 40 nM. The complementary charge interaction of MafI2(MGI-2B16B6) with the substrate binding surface of MafB2-CT(MGI-2B16B6) suggests that MafI2(MGI-2B16B6) inhibits MafB2-CT(MGI-2B16B6) by blocking access of RNA to the catalytic site. An in vitro enzymatic assay showed that MafB2-CT(MGI-2B16B6) has ribonuclease activity. Mutagenesis and cell toxicity assays demonstrated that His335, His402 and His409 are important for the toxic activity of MafB2-CT(MGI-2B16B6), suggesting that these residues are critical for its ribonuclease activity. These data provide structural and biochemical evidence that the origin of the toxic activity of MafB2(MGI-2B16B6) is the enzymatic activity degrading ribonucleotides.
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spelling pubmed-99709742023-03-01 Structural basis for the toxic activity of MafB2 from maf genomic island 2 (MGI-2) in N. meningitidis B16B6 Park, So Hyeon Jeong, Sun Ju Ha, Sung Chul Sci Rep Article The Maf polymorphic toxin system is involved in conflict between strains found in pathogenic Neisseria species such as Neisseria meningitidis and Neisseria gonorrhoeae. The genes encoding the Maf polymorphic toxin system are found in specific genomic islands called maf genomic islands (MGIs). In the MGIs, the MafB and MafI encode toxin and immunity proteins, respectively. Although the C-terminal region of MafB (MafB-CT) is specific for toxic activity, the underlying enzymatic activity that renders MafB-CT toxic is unknown in many MafB proteins due to lack of homology with domain of known function. Here we present the crystal structure of the MafB2-CT(MGI-2B16B6)/MafI2(MGI-2B16B6) complex from N. meningitidis B16B6. MafB2-CT(MGI-2B16B6) displays an RNase A fold similar to mouse RNase 1, although the sequence identity is only ~ 14.0%. MafB2-CT(MGI-2B16B6) forms a 1:1 complex with MafI2(MGI-2B16B6) with a Kd value of ~ 40 nM. The complementary charge interaction of MafI2(MGI-2B16B6) with the substrate binding surface of MafB2-CT(MGI-2B16B6) suggests that MafI2(MGI-2B16B6) inhibits MafB2-CT(MGI-2B16B6) by blocking access of RNA to the catalytic site. An in vitro enzymatic assay showed that MafB2-CT(MGI-2B16B6) has ribonuclease activity. Mutagenesis and cell toxicity assays demonstrated that His335, His402 and His409 are important for the toxic activity of MafB2-CT(MGI-2B16B6), suggesting that these residues are critical for its ribonuclease activity. These data provide structural and biochemical evidence that the origin of the toxic activity of MafB2(MGI-2B16B6) is the enzymatic activity degrading ribonucleotides. Nature Publishing Group UK 2023-02-27 /pmc/articles/PMC9970974/ /pubmed/36849501 http://dx.doi.org/10.1038/s41598-023-30528-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Park, So Hyeon
Jeong, Sun Ju
Ha, Sung Chul
Structural basis for the toxic activity of MafB2 from maf genomic island 2 (MGI-2) in N. meningitidis B16B6
title Structural basis for the toxic activity of MafB2 from maf genomic island 2 (MGI-2) in N. meningitidis B16B6
title_full Structural basis for the toxic activity of MafB2 from maf genomic island 2 (MGI-2) in N. meningitidis B16B6
title_fullStr Structural basis for the toxic activity of MafB2 from maf genomic island 2 (MGI-2) in N. meningitidis B16B6
title_full_unstemmed Structural basis for the toxic activity of MafB2 from maf genomic island 2 (MGI-2) in N. meningitidis B16B6
title_short Structural basis for the toxic activity of MafB2 from maf genomic island 2 (MGI-2) in N. meningitidis B16B6
title_sort structural basis for the toxic activity of mafb2 from maf genomic island 2 (mgi-2) in n. meningitidis b16b6
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9970974/
https://www.ncbi.nlm.nih.gov/pubmed/36849501
http://dx.doi.org/10.1038/s41598-023-30528-9
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