PhycoCosm, a comparative algal genomics resource.

Algae are a diverse, polyphyletic group of photosynthetic eukaryotes spanning nearly all eukaryotic lineages of life and collectively responsible for ∼50% of photosynthesis on Earth. Sequenced algal genomes, critical to understanding their complex biology, are growing in number and require efficient tools for analysis. PhycoCosm (https://phycocosm.jgi.doe.gov) is an algal multi-omics portal, developed by the US Department of Energy Joint Genome Institute to support analysis and distribution of algal genome sequences and other 'omics' data. PhycoCosm provides integration of genome sequence and annotation for >100 algal genomes with available multi-omics data and interactive web-based tools to enable algal research in bioenergy and the environment, encouraging community engagement and data exchange, and fostering new sequencing projects that will further these research goals.

Atlas of the Radical SAM Superfamily: Divergent Evolution of Function Using a "Plug and Play" Domain.

The radical SAM superfamily contains over 100,000 homologous enzymes that catalyze a remarkably broad range of reactions required for life, including metabolism, nucleic acid modification, and biogenesis of cofactors. While the highly conserved SAM-binding motif responsible for formation of the key 5'-deoxyadenosyl radical intermediate is a key structural feature that simplifies identification of superfamily members, our understanding of their structure-function relationships is complicated by the modular nature of their structures, which exhibit varied and complex domain architectures. To gain new insight about these relationships, we classified the entire set of sequences into similarity-based subgroups that could be visualized using sequence similarity networks. This superfamily-wide analysis reveals important features that had not previously been appreciated from studies focused on one or a few members. Functional information mapped to the networks indicates which members have been experimentally or structurally characterized, their known reaction types, and their phylogenetic distribution. Despite the biological importance of radical SAM chemistry, the vast majority of superfamily members have never been experimentally characterized in any way, suggesting that many new reactions remain to be discovered. In addition to 20 subgroups with at least one known function, we identified additional subgroups made up entirely of sequences of unknown function. Importantly, our results indicate that even general reaction types fail to track well with our sequence similarity-based subgroupings, raising major challenges for function prediction for currently identified and new members that continue to be discovered. Interactive similarity networks and other data from this analysis are available from the Structure-Function Linkage Database.

Structural effects of the L145Q, V157F, and R282W cancer-associated mutations in the p53 DNA-binding core domain.

The p53 tumor suppressor is a transcription factor involved in many important signaling pathways, such as apoptosis and cell-cycle arrest. In over half of human cancers, p53 function is compromised by a mutation in its gene. Mutations in the p53 DNA-binding core domain destabilize the structure and reduce DNA-binding activity. We performed molecular dynamics simulations at physiological temperature to study the structural and dynamic effects of the L145Q, V157F, and R282W cancer-associated mutations in comparison to the wild-type protein. While there were common regions of destabilization in the mutant simulations, structural changes particular to individual mutations were also observed. Significant backbone deviations of the H2 helix and S7-S8 loop were observed in all mutant simulations; the H2 helix binds to DNA. In addition, the L145Q and V157F mutations, which are located in the ß-sandwich core of the domain, disrupted the ß-sheet structure and the loop-sheet-helix motif. The R282W mutation caused distortion of the loop-sheet-helix motif, but otherwise this mutant was similar to the wild-type structure. The introduction of these mutations caused rearrangement of the DNA-binding surface, consistent with their reduced DNA-binding activity. The simulations reveal detailed effects of the mutations on the stability and dynamics of p53 that may provide insight for therapeutic approaches.