A proteome-wide structural systems approach reveals insights into protein families of all human herpesviruses
Year: 2024
Type: article
Abstract: Structure predictions have become invaluable tools, but viral proteins are absent from the EMBL/DeepMind AlphaFold database. Here, we provide proteome-wide structure predictions for all nine human herpesviruses and analyze them in depth with explicit scoring thresholds. By clustering these predictions into structural similarity groups, we identified new families, such as the HCMV UL112-113 cluster, which is conserved in alpha- and betaherpesviruses. A domain-level search found protein families consisting of subgroups with varying numbers of duplicated folds. Using large-scale structural similarity searches, we identified viral proteins with cellular folds, such as the HSV-1 US2 cluster possessing dihydrofolate reductase folds and the EBV BMRF2 cluster that might have emerged from cellular equilibrative nucleoside transporters. Our HerpesFolds database is available at https://www.herpesfolds.org/herpesfolds and displays all models and clusters through an interactive web interface. Here, we show that system-wide structure predictions can reveal homology between viral species and identify potential protein functions.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,790
Awards: G1925557638, G2875356657, G2899738257, G339059223, G3445821997, G3656803931, FOR 5200: Disrupt Evade Exploit: Steuerung der Genexpression und Wirtsantwort durch DNA Viren (DEEPDV), GRK 2771: Mensch und Mikrobe: Reorganisation von Zellkompartimenten und Molekülkomplexen während der Infektion, G4068377905, G4272965312, EXC 2155: RESIST Resolving Infection Susceptibility, G4466016162, Timestamping Integrative Approach to Understand Secondary Envelopment of Human Cytomegalovirus, G5186833673, G6207569021, G6387682778, G6781976155, Endogenous Human Herpesvirus: Germ line integration and effects on host cell and organism, G7786665414, G8693764584
OpenAlex ID: W4404723969