3MXH

Native structure of a c-di-GMP riboswitch from V. cholerae

Summary for 3MXH

• Entry DOI: 10.2210/pdb3mxh/pdb
• Related: 3IRW 3MUM 3MUR 3MUT 3MUV
• Descriptor: U1 small nuclear ribonucleoprotein A, c-di-GMP riboswitch, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: rna, riboswitch, c-di-gmp, rna binding protein-rna complex, rna binding protein/rna
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P09012
• Total number of polymer chains: 2
• Total formula weight: 42095.02

Authors

Strobel, S.A.,Smith, K.D. (deposition date: 2010-05-07, release date: 2010-08-25, Last modification date: 2023-09-06)

Primary citation

Smith, K.D.,Lipchock, S.V.,Livingston, A.L.,Shanahan, C.A.,Strobel, S.A.
Structural and biochemical determinants of ligand binding by the c-di-GMP riboswitch .
Biochemistry, 49:7351-7359, 2010

PubMed Abstract: The bacterial second messenger c-di-GMP is used in many species to control essential processes that allow the organism to adapt to its environment. The c-di-GMP riboswitch (GEMM) is an important downstream target in this signaling pathway and alters gene expression in response to changing concentrations of c-di-GMP. The riboswitch selectively recognizes its second messenger ligand primarily through contacts with two critical nucleotides. However, these two nucleotides are not the most highly conserved residues within the riboswitch sequence. Instead, nucleotides that stack with c-di-GMP and that form tertiary RNA contacts are the most invariant. Biochemical and structural evidence reveals that the most common natural variants are able to make alternative pairing interactions with both guanine bases of the ligand. Additionally, a high-resolution (2.3 A) crystal structure of the native complex reveals that a single metal coordinates the c-di-GMP backbone. Evidence is also provided that after transcription of the first nucleotide on the 3'-side of the P1 helix, which is predicted to be the molecular switch, the aptamer is functional for ligand binding. Although large energetic effects occur when several residues in the RNA are altered, mutations at the most conserved positions, rather than at positions that base pair with c-di-GMP, have the most detrimental effects on binding. Many mutants retain sufficient c-di-GMP affinity for the RNA to remain biologically relevant, which suggests that this motif is quite resilient to mutation.

PubMed: 20690679
DOI: 10.1021/bi100671e

Experimental method

X-RAY DIFFRACTION (2.3 Å)