Emerg Microbes Infect
Ebola virus (EBOV) transcription is essentially regulated via dynamic dephosphorylation of its viral transcription activator VP30 by the host phosphatase PP2A. The nucleoprotein NP has emerged as a third key player in the regulation of this process by recruiting both the regulatory subunit B56 of PP2A and its substrate VP30 to initiate VP30 dephosphorylation and hence viral transcription. Both binding sites are located in close proximity to each other in NP's C-terminal-disordered region. This study investigates NP's role in VP30 dephosphorylation and transcription activation, focusing on the spatial requirements of NP's binding sites. Increasing the distance between PP2A-B56 and VP30 at the NP interface revealed that close spatial and orientational contact is necessary for efficient VP30 dephosphorylation and viral transcription. Longer distances were lethal for recombinant EBOV except when a compensatory mutation, NP-T603I, occurred. This mutation, located between the NP binding sites for PP2A-B56 and VP30, fully restored functionality. Mass spectrometry showed that T603 is phosphorylated in recEBOV-NPwt virions. Mutational analysis indicated that T603I facilitates VP30 dephosphorylation in otherwise lethal recEBOV and that dynamic phosphorylation of NP-T603 is important for efficient primary viral transcription in the WT context. These findings emphasize the critical and evolutionarily pressured interplay between VP30 and PP2A-B56 within the NP C-terminal-disordered region and highlight the important role of NP on the regulation of viral transcription during the EBOV life cycle.
Keywords: Ebola virus; VP30; host phosphatase PP2A; nucleoprotein; phosphorylation; regulation; viral transcription.
Lisätieto fosfataasisa PP2A-B56.p.pl?gene=PPP2R5A&keywords=PP2A-B56
Aliases for PPP2R5A Gene
- GeneCards Symbol: PPP2R5A 2
- Protein Phosphatase 2 Regulatory Subunit B''Alpha 2
- Protein Phosphatase 2 Regulatory Subunit B'Alpha 2 3 5
- B56alpha 2 3 5
- PR61A 2 3 5
- B56A 2 3 5
- Serine/Threonine-Protein Phosphatase 2A 56 KDa Regulatory Subunit Alpha Isoform
The product of this gene belongs to the phosphatase 2A regulatory subunit B family. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes an alpha isoform of the regulatory subunit B56 subfamily. Alternative transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Dec 2010]
GeneCards Summary for PPP2R5A Gene
PPP2R5A (Protein Phosphatase 2 Regulatory Subunit B''Alpha) is a Protein Coding gene. Diseases associated with PPP2R5A include Cardiac Arrhythmia, Ankyrin-B-Related and Progressive Familial Heart Block, Type Ii. Among its related pathways are CTNNB1 S45 mutants aren't phosphorylated and EML4 and NUDC in mitotic spindle formation. Gene Ontology (GO) annotations related to this gene include binding and protein phosphatase regulator activity. An important paralog of this gene is PPP2R5E.
UniProtKB/Swiss-Prot Summary for PPP2R5A Gene
The B regulatory subunit might modulate substrate selectivity and catalytic activity, and might also direct the localization of the catalytic enzyme to a particular subcellular compartment. ( 2A5A_HUMAN,Q15172 )
Gene Families for PPP2R5A Gene
- Predicted intracellular proteins
Protein Domains for PPP2R5A Gene
- Protein phosphatase 2A, regulatory B subunit (B56 family)
Suggested Antigen Peptide Sequences for PPP2R5A Gene
- PP2A B subunit isoform R5-alpha (2A5A_HUMAN)
- cDNA FLJ51383, highly similar to Serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform (B7Z7L2_HUMAN)
Inga kommentarer:
Skicka en kommentar