Publication Date:
2012-10-16
Description:
Structures of riboswitch receptor domains bound to their effector have shown how messenger RNAs recognize diverse small molecules, but mechanistic details linking the structures to the regulation of gene expression remain elusive. To address this, here we solve 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, to our knowledge, riboswitch crystal structure detailing how the receptor and regulatory domains communicate in a ligand-dependent fashion to regulate mRNA expression.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518761/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3518761/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Johnson, James E Jr -- Reyes, Francis E -- Polaski, Jacob T -- Batey, Robert T -- 1S10RR026516/RR/NCRR NIH HHS/ -- F32 GM095121/GM/NIGMS NIH HHS/ -- F32GM095121/GM/NIGMS NIH HHS/ -- GM073850/GM/NIGMS NIH HHS/ -- R01 GM073850/GM/NIGMS NIH HHS/ -- S10 RR026516/RR/NCRR NIH HHS/ -- England -- Nature. 2012 Dec 6;492(7427):133-7. doi: 10.1038/nature11607. Epub 2012 Oct 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry and Biochemistry, University of Colorado at Boulder, Boulder, Colorado 80309-0596, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23064232" target="_blank"〉PubMed〈/a〉
Keywords:
Base Sequence
;
Calorimetry
;
Crystallography, X-Ray
;
Escherichia coli/genetics
;
Gene Expression Regulation/drug effects
;
Hydrogen Bonding/drug effects
;
Ligands
;
Models, Molecular
;
Nucleic Acid Conformation/*drug effects
;
RNA, Bacterial/genetics
;
RNA, Messenger/*chemistry/drug effects/genetics/metabolism
;
Riboswitch/*drug effects/genetics
;
Thermodynamics
;
Vitamin B 12/*chemistry/metabolism/*pharmacology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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