Schematic representation of Mre11 (Panel A) and Rad50 (Panel B) domains.

<p>(A) Mre11 has five phosphodiesterase motifs (green), 6 dsDNA recognition loop (yellow) and hydrophobic surface clusters (grey) (B) Rad50 has a bipartite ATPase domain: Walker A (red), Walker B (pale red), Q-loop (light blue), ABC-Signature motif (orange), histidine switch (green H) and has a Zinc-hook (purple).</p

The flowchart of the Metagenomic Telescope applied to DNA repair enzymes.

<p>The flowchart of the Metagenomic Telescope applied to DNA repair enzymes.</p

The original projection (upper panel) compared to the scheme of the Metagenomic Telescope (lower panel).

<p>Projection 1 discovers genes or proteins in the metagenome that probably have similar function as the well-known starting proteins in front of the objective lens on the right hand side. Projection 2 directly identifies these proteins within the proteomes of the model organisms (as a set of UniProt accession numbers).</p

Identification of a novel dUTPase-like protein in the mouse proteome using the Metagenomic Telescope.

<p>Panel A shows an alignment (created by ClustalW) between the mouse dUTPase sequence (cyan) and the novel hit associated with the Uniprot accession number Q3TL09 (purple color indicates the part of this latter sequence that could be modeled in 3D using SwissModel or MUSTER). The conserved dUTPase motifs are shown in yellow. Panel B illustrates the structural alignment between human dUTPase (cyan) and the Q3TL09 modeled structure (purple) (at the subunit level). Panel C shows one of the models for Q3TL09 created by MUSTER software (purple), in this case the trimeric structure characteristic of dUTPases is shown (monomers are in shades of blue: cyan, royal blue and grayish blue). Protein structural models are shown in ribbon diagrams (PyMol).</p

Protein families and proteomes used in the present study.

<p>Protein families and proteomes used in the present study.</p

New telescopic hits associated with a role in transcription regulation.

<p>Using Rad50 sequences to build the starting HMM model, the Metagenomic Telescope approach identified the new telescopic hits listed in the table.</p

Original and telescopic hits for the Rad50 family.

<p>Panel A. Number of hits identified in the various eukaryotic model organisms after the original and the telescopic projections. Panel B. Distribution of genome ontology terms within the different hits. Note that new genome ontology classes can be observed in the telescopic hits.</p

Polar inter-chain interactions between L3, αA and N-terminal regions in homology models of both enzyme variants.

<p>N-terminal region consists of residues 581–620 (cf. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0129632#pone.0129632.g001" target="_blank">Fig 1A</a>).</p><p>Polar inter-chain interactions between L3, αA and N-terminal regions in homology models of both enzyme variants.</p

Inter-subunit interaction energies during molecular dynamics simulations.

<p>Interaction energies are calculated as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0129632#pone.0129632.e001" target="_blank">Eq 1</a> and represented by black line in case of <i>Pf</i>CCT MΔK^WT and by grey line in case of <i>Pf</i>CCT MΔK^R681H, respectively.</p

Polar interactions at the dimer interface of <i>Pf</i>CCT MΔK^WT and <i>Pf</i>CCT MΔK^R681H involving ⁶⁸¹RWVD⁶⁸⁴.

<p>A) Direct interactions harbouring ⁶⁸¹RWVD⁶⁸⁴ signature sequence motif in <i>Pf</i>CCT MΔK^WT. The residues involved in the inter-chain interaction are shown in stick representation, and interactions are indicated by pink dashed lines. Characteristic dimer interface distances d(R681, CA - H679’, O) and d(I680, CA - I680’, N) are denoted by blue double-headed arrows. Residues in chain B are marked with apostrophes. B) Direct interactions harbouring the ⁶⁸¹HWVD⁶⁸⁴ mutated signature sequence motif <i>Pf</i>CCT MΔK^R681H. The residues involved in the inter-chain interaction are shown in stick representation, and interactions are indicated by pink dashed lines. Characteristic dimer interface distances d(H681, CA - H679’, O) and d(I680, CA - I680’, N) are denoted by blue double-headed arrows. Residues in chain B are marked with apostrophes.</p