RNA structure comparison, motif search and discovery using a reduced representation of RNA conformational space - PubMed (original) (raw)

Comparative Study

. 2003 Aug 15;31(16):4755-61.

doi: 10.1093/nar/gkg682.

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Comparative Study

RNA structure comparison, motif search and discovery using a reduced representation of RNA conformational space

Carlos M Duarte et al. Nucleic Acids Res. 2003.

Abstract

Given the wealth of new RNA structures and the growing list of RNA functions in biology, it is of great interest to understand the repertoire of RNA folding motifs. The ability to identify new and known motifs within novel RNA structures, to compare tertiary structures with one another and to quantify the characteristics of a given RNA motif are major goals in the field of RNA research; however, there are few systematic ways to address these issues. Using a novel approach for visualizing and mathematically describing macromolecular structures, we have developed a means to quantitatively describe RNA molecules in order to rapidly analyze, compare and explore their features. This approach builds on the alternative eta,theta convention for describing RNA torsion angles and is executed using a new program called PRIMOS. Applying this methodology, we have successfully identified major regions of conformational change in the 50S and 30S ribosomal subunits, we have developed a means to search the database of RNA structures for the prevalence of known motifs and we have classified and identified new motifs. These applications illustrate the powerful capabilities of our new RNA structural convention, and they suggest future adaptations with important implications for bioinformatics and structural genomics.

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Figures

Figure 1

Figure 1

RNA pseudotorsions. RNA trinucleotide (blue) in Type-A conformation with virtual bonds (red) connecting atoms P to C4′ and C4′ to P. Each of these virtual bonds is the central bond of the corresponding pseudotorsions, η (C4′n_-1–P_n_–C4′_n_–P_n+1) and θ (P_n_–C4′n_–P_n+1–C4′n+1).

Figure 2

Figure 2

Path-annotated η–θ plots. (a) The path through sequence space of the η–θ values for a typical UUCG tetraloop (PDB code: 1F7Y) (38); (b) the same type of path for D5 (PDB code: 1KXK) (39).

Figure 3

Figure 3

RNA worm of D5. The worm is plotted with projections onto the η-sequence plane and the θ-sequence plane. Also shown is the actual D5 structure. Helices (blue) are distinguishable from the non-helical features (red), bulge and GAAA tetraloop.

Figure 4

Figure 4

Ribosomal comparisons identify structural differences. (a) The Δ(η,θ) per nucleotide between T30S bound by an mRNA fragment (PDB code: 1FJF) and the same subunit also bound by paromomycin and a tRNA ASL (PDB code: 1KQS). The line at 25° indicates a threshold above which nucleotides are considered to have different conformations in each complex. Some regions undergoing conformational changes between the complexes are indicated: the A-site (A1492), the P-site (C1397) and a site in the platform domain (C748). (b) The comparison of unbound H50S (PDB code: 1JJ2) and H50S in a pre-translocational intermediate state (PDB code: 1KQS). Indicated regions are at the A-site (U2620) and P-site (A2637). (c) The comparison of D50S bound by clarithromycin (PDB code: 1K00) and bound by chloramphenicol (PDB code: 1K01). Indicated regions interact with clarithromycin (A2041, U2588) or chloramphenicol (U2483).

Figure 5

Figure 5

Conformational flexibility at A2637. Overlays of the G2634–U2640 portions of the H50S subunits from four different complexes. Positions C2636 and A2637 of unbound H50S (red), pre-translocation H50S (green), A-site ligand H50S (blue) and P-site ligand H50S (pink) are colored for reference. Despite the conformational heterogeneity at A2637, the 5′ and 3′ ends (gray) of the each of the structures are essentially superimposable.

Figure 6

Figure 6

Two types of S-motifs. (a) Characteristic RNA worms for analogous portions of S1 (black) and S2 (red) motifs shown as in Figure 3. (b) S1-motif structure with backbone ribbon (PDB code: 480D). Nucleotides for the S1 worm (U2653–U2656) are in black. (c) S2-motif structure (PDB code: 1JJ2). Nucleotides for the S2 worm (G892–A895) are in red.

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