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Recognition of the bacterial alarmone ZMP through long-distance association of two RNA subdomains.

ABSTRACT: The bacterial alarmone 5-aminoimidazole-4-carboxamide riboside 5'-triphosphate (AICAR triphosphate or ZTP), derived from the monophosphorylated purine precursor ZMP, accumulates during folate starvation. ZTP regulates genes involved in purine and folate metabolism through a cognate riboswitch. The linker connecting this riboswitch's two subdomains varies in length by over 100 nucleotides. We report the cocrystal structure of the Fusobacterium ulcerans riboswitch bound to ZMP, which spans the two subdomains whose interface also comprises a pseudoknot and ribose zipper. The riboswitch recognizes the carboxamide oxygen of ZMP through an unprecedented inner-sphere coordination with a Mg(2+) ion. We show that the affinity of the riboswitch for ZMP is modulated by the linker length. Notably, ZMP can simultaneously bind to the two subdomains even when they are synthesized as separate RNAs. The ZTP riboswitch demonstrates how specific small-molecule binding can drive association of distant noncoding-RNA domains to regulate gene expression.

SUBMITTER: Jones CP

PROVIDER: S-EPMC4824399 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Recognition of the bacterial alarmone ZMP through long-distance association of two RNA subdomains.

Jones Christopher P CP Ferré-D'Amaré Adrian R AR

Nature structural & molecular biology 20150817 9

The bacterial alarmone 5-aminoimidazole-4-carboxamide riboside 5'-triphosphate (AICAR triphosphate or ZTP), derived from the monophosphorylated purine precursor ZMP, accumulates during folate starvation. ZTP regulates genes involved in purine and folate metabolism through a cognate riboswitch. The linker connecting this riboswitch's two subdomains varies in length by over 100 nucleotides. We report the cocrystal structure of the Fusobacterium ulcerans riboswitch bound to ZMP, which spans the two ...[more]

PMID: 26280533

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Project description:UnlabelledSelf- versus nonself-recognition in bacteria has been described recently through genetic analyses in multiple systems; however, understanding of the biochemical properties and mechanisms of recognition-determinant proteins remains limited. Here we extend the molecular and biochemical understanding of two recognition-determinant proteins in bacteria. We have found that a heterotypic complex is formed between two bacterial self-recognition proteins, IdsD and IdsE, the genes of which have been shown to genetically encode the determinants for strain-specific identity in the opportunistic bacterial pathogen Proteus mirabilis. This IdsD-IdsE complex forms independently of other P. mirabilis-encoded self-recognition proteins. We have also shown that the binding between IdsD and IdsE is strain- and allele-specific. The specificity for interactions is encoded within a predicted membrane-spanning subdomain within each protein that contains stretches of unique amino acids in each P. mirabilis variant. Finally, we have demonstrated that this in vitro IdsD-IdsE binding interaction correlates to in vivo population identity, suggesting that the binding interactions between IdsD and IdsE are part of a cellular pathway that underpins self-recognition behavior in P. mirabilis and drives bacterial population sociality.ImportanceHere we demonstrate that two proteins, the genes of which were genetically shown to encode determinants of self-identity in bacteria, bind in vitro in an allele-restricted interaction, suggesting that molecular recognition between these two proteins is a mechanism underpinning self-recognition behaviors in P. mirabilis. Binding specificity in each protein is encapsulated in a variable region subdomain that is predicted to span the membrane, suggesting that the interaction occurs in the cell envelope. Furthermore, conversion of binding affinities in vitro correlates with conversion of self-identity in vivo, suggesting that this molecular recognition might help to drive population behaviors.

Dataset Information

Recognition of the bacterial alarmone ZMP through long-distance association of two RNA subdomains.

Publications

Recognition of the bacterial alarmone ZMP through long-distance association of two RNA subdomains.

Similar Datasets

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