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B(12) cofactors directly stabilize an mRNA regulatory switch

Structures of riboswitch receptor domains bound to their effector have revealed how mRNAs recognize diverse small molecules, but mechanistic details into its linkage with regulation of gene expression remain elusive(1,2). To address this, we solved crystal structures of two different classes of coba...

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Detalles Bibliográficos
Autores principales: Johnson, James E., Reyes, Francis E., Polaski, Jacob T., Batey, Robert T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518761/
https://www.ncbi.nlm.nih.gov/pubmed/23064232
http://dx.doi.org/10.1038/nature11607
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author Johnson, James E.
Reyes, Francis E.
Polaski, Jacob T.
Batey, Robert T.
author_facet Johnson, James E.
Reyes, Francis E.
Polaski, Jacob T.
Batey, Robert T.
author_sort Johnson, James E.
collection PubMed
description Structures of riboswitch receptor domains bound to their effector have revealed how mRNAs recognize diverse small molecules, but mechanistic details into its linkage with regulation of gene expression remain elusive(1,2). To address this, we solved crystal structures of two different classes of cobalamin (vitamin B(12)) binding riboswitches that include the structural switch of the downstream regulatory domain. These classes share a common cobalamin-binding core, but use distinct peripheral extensions to recognize different B(12) derivatives. In each case, recognition is accomplished through shape complementarity between the RNA and cobalamin with relatively few hydrogen bonding interactions that typically govern RNA-small molecule recognition. We show that a composite cobalamin/RNA scaffold stabilizes an unusual long-range intramolecular kissing-loop interaction that controls mRNA expression. This is the first riboswitch crystal structure detailing how the receptor and regulatory domains communicate in a ligand-dependent fashion to regulate mRNA expression.
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spelling pubmed-35187612013-06-06 B(12) cofactors directly stabilize an mRNA regulatory switch Johnson, James E. Reyes, Francis E. Polaski, Jacob T. Batey, Robert T. Nature Article Structures of riboswitch receptor domains bound to their effector have revealed how mRNAs recognize diverse small molecules, but mechanistic details into its linkage with regulation of gene expression remain elusive(1,2). To address this, we solved crystal structures of two different classes of cobalamin (vitamin B(12)) binding riboswitches that include the structural switch of the downstream regulatory domain. These classes share a common cobalamin-binding core, but use distinct peripheral extensions to recognize different B(12) derivatives. In each case, recognition is accomplished through shape complementarity between the RNA and cobalamin with relatively few hydrogen bonding interactions that typically govern RNA-small molecule recognition. We show that a composite cobalamin/RNA scaffold stabilizes an unusual long-range intramolecular kissing-loop interaction that controls mRNA expression. This is the first riboswitch crystal structure detailing how the receptor and regulatory domains communicate in a ligand-dependent fashion to regulate mRNA expression. 2012-10-14 2012-12-06 /pmc/articles/PMC3518761/ /pubmed/23064232 http://dx.doi.org/10.1038/nature11607 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Johnson, James E.
Reyes, Francis E.
Polaski, Jacob T.
Batey, Robert T.
B(12) cofactors directly stabilize an mRNA regulatory switch
title B(12) cofactors directly stabilize an mRNA regulatory switch
title_full B(12) cofactors directly stabilize an mRNA regulatory switch
title_fullStr B(12) cofactors directly stabilize an mRNA regulatory switch
title_full_unstemmed B(12) cofactors directly stabilize an mRNA regulatory switch
title_short B(12) cofactors directly stabilize an mRNA regulatory switch
title_sort b(12) cofactors directly stabilize an mrna regulatory switch
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518761/
https://www.ncbi.nlm.nih.gov/pubmed/23064232
http://dx.doi.org/10.1038/nature11607
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