PDBsum entry 2gdi

RNA

PDB id

2gdi

Contents

			DNA/RNA

			Ligands

					TPP ×2

			Metals

					_NA ×2


					__K ×3


					_MG ×6

			Waters ×312

References listed in PDB file

Key reference

Title

Structural basis for gene regulation by a thiamine pyrophosphate-Sensing riboswitch.

Authors

A.Serganov, A.Polonskaia, A.T.Phan, R.R.Breaker, D.J.Patel.

Ref.

Nature, 2006, 441, 1167-1171. [DOI no: 10.1038/nature04740]

PubMed id

16728979

Abstract

Riboswitches are metabolite-sensing RNAs, typically located in the non-coding portions of messenger RNAs, that control the synthesis of metabolite-related proteins. Here we describe a 2.05 angstroms crystal structure of a riboswitch domain from the Escherichia coli thiM mRNA that responds to the coenzyme thiamine pyrophosphate (TPP). TPP is an active form of vitamin B1, an essential participant in many protein-catalysed reactions. Organisms from all three domains of life, including bacteria, plants and fungi, use TPP-sensing riboswitches to control genes responsible for importing or synthesizing thiamine and its phosphorylated derivatives, making this riboswitch class the most widely distributed member of the metabolite-sensing RNA regulatory system. The structure reveals a complex folded RNA in which one subdomain forms an intercalation pocket for the 4-amino-5-hydroxymethyl-2-methylpyrimidine moiety of TPP, whereas another subdomain forms a wider pocket that uses bivalent metal ions and water molecules to make bridging contacts to the pyrophosphate moiety of the ligand. The two pockets are positioned to function as a molecular measuring device that recognizes TPP in an extended conformation. The central thiazole moiety is not recognized by the RNA, which explains why the antimicrobial compound pyrithiamine pyrophosphate targets this riboswitch and downregulates the expression of thiamine metabolic genes. Both the natural ligand and its drug-like analogue stabilize secondary and tertiary structure elements that are harnessed by the riboswitch to modulate the synthesis of the proteins coded by the mRNA. In addition, this structure provides insight into how folded RNAs can form precision binding pockets that rival those formed by protein genetic factors.



	Figure 2. Figure 2: Structure and interactions in the TPP-binding pocket. a, Stereo view of the central region of the complex containing bound TPP. b, View of TPP, coordinated Mg^2+ ions (magenta) and water (blue spheres) in the binding pocket. c, Details of the interactions between the HMP ring and RNA. d, Hydrogen bonding between Mg^2+ ions and RNA.		Figure 3. Figure 3: Tertiary interactions defining TPP riboswitch structure and accessibility to the binding pocket. a, Interaction between J3/2 and P2, mediated by the HMP ring. b, Stabilization of the J2-4 junction by two stacked tetrads (in space-filling representation). c, Interactions between L5 and P3 mediated by three K^+ ions (red spheres). d, Surface representation of RNA and accessibility to the TPP-binding pocket. TPP is depicted in a stick and mesh representation.

	Headers