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The structure of CrgA from Neisseria meningitidis reveals a new octameric assembly state for LysR transcriptional regulators

LysR-type transcriptional regulators (LTTRs) form the largest family of bacterial regulators acting as both auto-repressors and activators of target promoters, controlling operons involved in a wide variety of cellular processes. The LTTR, CrgA, from the human pathogen Neisseria meningitidis, is upr...

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Autores principales: Sainsbury, Sarah, Lane, Laura A., Ren, Jingshan, Gilbert, Robert J., Saunders, Nigel J., Robinson, Carol V., Stuart, David I., Owens, Raymond J.
Formato: Texto
Lenguaje:English
Publicado: Oxford University Press 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724274/
https://www.ncbi.nlm.nih.gov/pubmed/19474343
http://dx.doi.org/10.1093/nar/gkp445
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author Sainsbury, Sarah
Lane, Laura A.
Ren, Jingshan
Gilbert, Robert J.
Saunders, Nigel J.
Robinson, Carol V.
Stuart, David I.
Owens, Raymond J.
author_facet Sainsbury, Sarah
Lane, Laura A.
Ren, Jingshan
Gilbert, Robert J.
Saunders, Nigel J.
Robinson, Carol V.
Stuart, David I.
Owens, Raymond J.
author_sort Sainsbury, Sarah
collection PubMed
description LysR-type transcriptional regulators (LTTRs) form the largest family of bacterial regulators acting as both auto-repressors and activators of target promoters, controlling operons involved in a wide variety of cellular processes. The LTTR, CrgA, from the human pathogen Neisseria meningitidis, is upregulated during bacterial–host cell contact. Here, we report the crystal structures of both regulatory domain and full-length CrgA, the first of a novel subclass of LTTRs that form octameric rings. Non-denaturing mass spectrometry analysis and analytical ultracentrifugation established that the octameric form of CrgA is the predominant species in solution in both the presence and absence of an oligonucleotide encompassing the CrgA-binding sequence. Furthermore, analysis of the isolated CrgA–DNA complex by mass spectrometry showed stabilization of a double octamer species upon DNA binding. Based on the observed structure and the mass spectrometry findings, a model is proposed in which a hexadecameric array of two CrgA oligomers binds to its DNA target site.
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spelling pubmed-27242742009-08-18 The structure of CrgA from Neisseria meningitidis reveals a new octameric assembly state for LysR transcriptional regulators Sainsbury, Sarah Lane, Laura A. Ren, Jingshan Gilbert, Robert J. Saunders, Nigel J. Robinson, Carol V. Stuart, David I. Owens, Raymond J. Nucleic Acids Res Structural Biology LysR-type transcriptional regulators (LTTRs) form the largest family of bacterial regulators acting as both auto-repressors and activators of target promoters, controlling operons involved in a wide variety of cellular processes. The LTTR, CrgA, from the human pathogen Neisseria meningitidis, is upregulated during bacterial–host cell contact. Here, we report the crystal structures of both regulatory domain and full-length CrgA, the first of a novel subclass of LTTRs that form octameric rings. Non-denaturing mass spectrometry analysis and analytical ultracentrifugation established that the octameric form of CrgA is the predominant species in solution in both the presence and absence of an oligonucleotide encompassing the CrgA-binding sequence. Furthermore, analysis of the isolated CrgA–DNA complex by mass spectrometry showed stabilization of a double octamer species upon DNA binding. Based on the observed structure and the mass spectrometry findings, a model is proposed in which a hexadecameric array of two CrgA oligomers binds to its DNA target site. Oxford University Press 2009-08 2009-05-27 /pmc/articles/PMC2724274/ /pubmed/19474343 http://dx.doi.org/10.1093/nar/gkp445 Text en © 2009 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Structural Biology
Sainsbury, Sarah
Lane, Laura A.
Ren, Jingshan
Gilbert, Robert J.
Saunders, Nigel J.
Robinson, Carol V.
Stuart, David I.
Owens, Raymond J.
The structure of CrgA from Neisseria meningitidis reveals a new octameric assembly state for LysR transcriptional regulators
title The structure of CrgA from Neisseria meningitidis reveals a new octameric assembly state for LysR transcriptional regulators
title_full The structure of CrgA from Neisseria meningitidis reveals a new octameric assembly state for LysR transcriptional regulators
title_fullStr The structure of CrgA from Neisseria meningitidis reveals a new octameric assembly state for LysR transcriptional regulators
title_full_unstemmed The structure of CrgA from Neisseria meningitidis reveals a new octameric assembly state for LysR transcriptional regulators
title_short The structure of CrgA from Neisseria meningitidis reveals a new octameric assembly state for LysR transcriptional regulators
title_sort structure of crga from neisseria meningitidis reveals a new octameric assembly state for lysr transcriptional regulators
topic Structural Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724274/
https://www.ncbi.nlm.nih.gov/pubmed/19474343
http://dx.doi.org/10.1093/nar/gkp445
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