To be or not to be phosphorylated: Understanding the role of Ebola virus nucleoprotein in the dynamic interplay with the transcriptional activator VP30 and the host phosphatase PP2A-B56 DOI Creative Commons
Lennart Kämper,

I Kuhl,

Melina Vallbracht

et al.

Emerging Microbes & Infections, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 27, 2024

Ebola virus (EBOV) transcription is essentially regulated via dynamic dephosphorylation of its viral activator VP30 by the host phosphatase PP2A. The nucleoprotein NP has emerged as a third key player in regulation this process recruiting both regulatory subunit B56 PP2A and substrate to initiate hence transcription. Both binding sites are located close proximity each other NP's C-terminal disordered region. This study investigates role activation, focusing on spatial requirements sites. Increasing distance between PP2A-B56 at interface revealed that orientational contact necessary for efficient Longer distances were lethal recombinant EBOV except when compensatory mutation, NP-T603I, occurred. VP30, fully restored functionality. Mass spectrometry showed T603 phosphorylated recEBOV-NPwt virions. Mutational analysis indicated T603I facilitates otherwise recEBOV phosphorylation NP-T603 important primary WT context. These findings emphasize critical evolutionarily pressured interplay within region highlight during life cycle.

Language: Английский

BFVD - a large repository of predicted viral protein structures DOI Creative Commons

Rachel Seongeun Kim,

Eli Levy Karin, Martin Steinegger

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 9, 2024

The AlphaFold Protein Structure Database (AFDB) is the largest repository of accurately predicted structures with taxonomic labels. Despite providing predictions for over 214 million UniProt entries, AFDB does not cover viral sequences, severely limiting their study. To bridge this gap, we created Big Fantastic Virus (BFVD), a 351,242 protein by applying ColabFold to sequence representatives UniRef30 clusters. BFVD holds unique repertoire as 63% its entries show no or low structural similarity existing repositories. We demonstrate how substantially enhances fraction annotated bacteriophage proteins compared sequence-based annotation using Bakta. In that, on par AFDB, while holding nearly three orders magnitude fewer structures. an important virus-specific expansion structure repositories, offering new opportunities advance research. freely available at https://bfvd.steineggerlab.workers.dev/

Language: Английский

Citations

4
To be or not to be phosphorylated: Understanding the role of Ebola virus nucleoprotein in the dynamic interplay with the transcriptional activator VP30 and the host phosphatase PP2A-B56 DOI Creative Commons
Lennart Kämper,

I Kuhl,

Melina Vallbracht

et al.

Emerging Microbes & Infections, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 27, 2024

Ebola virus (EBOV) transcription is essentially regulated via dynamic dephosphorylation of its viral activator VP30 by the host phosphatase PP2A. The nucleoprotein NP has emerged as a third key player in regulation this process recruiting both regulatory subunit B56 PP2A and substrate to initiate hence transcription. Both binding sites are located close proximity each other NP's C-terminal disordered region. This study investigates role activation, focusing on spatial requirements sites. Increasing distance between PP2A-B56 at interface revealed that orientational contact necessary for efficient Longer distances were lethal recombinant EBOV except when compensatory mutation, NP-T603I, occurred. VP30, fully restored functionality. Mass spectrometry showed T603 phosphorylated recEBOV-NPwt virions. Mutational analysis indicated T603I facilitates otherwise recEBOV phosphorylation NP-T603 important primary WT context. These findings emphasize critical evolutionarily pressured interplay within region highlight during life cycle.

Language: Английский

Citations

0