PMID- 19898477 OWN - NLM STAT- MEDLINE DCOM- 20091230 LR - 20211020 IS - 1545-9985 (Electronic) IS - 1545-9993 (Print) IS - 1545-9985 (Linking) VI - 16 IP - 12 DP - 2009 Dec TI - Structural basis of ligand binding by a c-di-GMP riboswitch. PG - 1218-23 LID - 10.1038/nsmb.1702 [doi] AB - The second messenger signaling molecule bis-(3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP) regulates many processes in bacteria, including motility, pathogenesis and biofilm formation. c-di-GMP-binding riboswitches are important downstream targets in this signaling pathway. Here we report the crystal structure, at 2.7 A resolution, of a c-di-GMP riboswitch aptamer from Vibrio cholerae bound to c-di-GMP, showing that the ligand binds within a three-helix junction that involves base-pairing and extensive base-stacking. The symmetric c-di-GMP is recognized asymmetrically with respect to both the bases and the backbone. A mutant aptamer was engineered that preferentially binds the candidate signaling molecule c-di-AMP over c-di-GMP. Kinetic and structural data suggest that genetic regulation by the c-di-GMP riboswitch is kinetically controlled and that gene expression is modulated through the stabilization of a previously unidentified P1 helix, illustrating a direct mechanism for c-di-GMP signaling. FAU - Smith, Kathryn D AU - Smith KD AD - Department of Chemistry, Yale University, New Haven, Connecticut, USA. FAU - Lipchock, Sarah V AU - Lipchock SV FAU - Ames, Tyler D AU - Ames TD FAU - Wang, Jimin AU - Wang J FAU - Breaker, Ronald R AU - Breaker RR FAU - Strobel, Scott A AU - Strobel SA LA - eng GR - GM02278/GM/NIGMS NIH HHS/United States GR - P30 EB009998/EB/NIBIB NIH HHS/United States GR - P01 GM022778/GM/NIGMS NIH HHS/United States GR - P01 GM022778-347368/GM/NIGMS NIH HHS/United States GR - P01 GM022778-310003/GM/NIGMS NIH HHS/United States GR - P01 GM022778-357368/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20091108 PL - United States TA - Nat Struct Mol Biol JT - Nature structural & molecular biology JID - 101186374 RN - 0 (Dinucleoside Phosphates) RN - 0 (Intercalating Agents) RN - 0 (RNA, Bacterial) RN - 0 (cyclic diadenosine phosphate) RN - 61093-23-0 (bis(3',5')-cyclic diguanylic acid) RN - H2D2X058MU (Cyclic GMP) SB - IM CIN - Nat Struct Mol Biol. 2009 Dec;16(12):1201. PMID: 19956202 MH - Base Pairing MH - Crystallography, X-Ray MH - Cyclic GMP/*analogs & derivatives/chemistry/metabolism MH - Dinucleoside Phosphates/metabolism MH - *Gene Expression Regulation, Bacterial MH - Intercalating Agents MH - Kinetics MH - Models, Molecular MH - Nucleic Acid Conformation MH - RNA, Bacterial/*chemistry/genetics/*metabolism MH - Scattering, Small Angle MH - Second Messenger Systems/*physiology MH - Vibrio cholerae/chemistry/*physiology PMC - PMC2850612 MID - NIHMS191190 EDAT- 2009/11/10 06:00 MHDA- 2009/12/31 06:00 PMCR- 2010/06/01 CRDT- 2009/11/10 06:00 PHST- 2009/07/13 00:00 [received] PHST- 2009/09/15 00:00 [accepted] PHST- 2009/11/10 06:00 [entrez] PHST- 2009/11/10 06:00 [pubmed] PHST- 2009/12/31 06:00 [medline] PHST- 2010/06/01 00:00 [pmc-release] AID - nsmb.1702 [pii] AID - 10.1038/nsmb.1702 [doi] PST - ppublish SO - Nat Struct Mol Biol. 2009 Dec;16(12):1218-23. doi: 10.1038/nsmb.1702. Epub 2009 Nov 8.