PDBsum entry 2gdi

RNA

PDB id: 2gdi

Contents

DNA/RNA

Ligands

TPP ×2

Metals

_NA ×2

__K ×3

_MG ×6

Waters ×312

PDB id:

2gdi

Name:

RNA

Title:

Crystal structure of thiamine pyrophosphate-specific riboswitch in complex with thiamine pyrophosphate

Structure:

Tpp riboswitch. Chain: x, y. Fragment: sensing domain. Engineered: yes

Source:

Synthetic: yes. Other_details: RNA was prepared by in vitro transcription

Resolution:

2.05Å R-factor: 0.210 R-free: 0.241

Authors:

A.Serganov

Key ref:

A.Serganov et al. (2006). Structural basis for gene regulation by a thiamine pyrophosphate-sensing riboswitch. Nature, 441, 1167-1171. PubMed id: 16728979 DOI: 10.1038/nature04740

Date:

16-Mar-06 Release date: 04-Jul-06

DNA/RNA chains

GTP-G-A-C-U-C-G-G-G-G-U-G-C-C-C-U-U-C-U-G-C-G-U-G-A-A-G-G-C-U-G-A-G-A-A-A-U-A- 80 bases

GTP-G-A-C-U-C-G-G-G-G-U-G-C-C-C-U-U-C-U-G-C-G-U-G-A-A-G-G-C-U-G-A-G-A-A-A-U-A- 80 bases

DOI no: 10.1038/nature04740

Nature 441:1167-1171 (2006)

PubMed id: 16728979

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

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

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.

Selected figure(s)

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.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2006, 441, 1167-1171) copyright 2006.

Figures were selected by an automated process.