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Prototype foamy virus intasome aggregation is mediated by outer protein domains and prevented by protocatechuic acid.

Authors :
Jones ND
Mackler RM
Lopez MA Jr
Baltierra-Jasso LE
Altman MP
Senavirathne G
Yoder KE
Source :
Scientific reports [Sci Rep] 2019 Jan 15; Vol. 9 (1), pp. 132. Date of Electronic Publication: 2019 Jan 15.
Publication Year :
2019

Abstract

The integrase (IN) enzyme of retrovirus prototype foamy virus (PFV) consists of four domains: amino terminal extension (NED), amino terminus (NTD), catalytic core (CCD), and carboxyl terminus domains (CTD). A tetramer of PFV IN with two viral DNA ends forms the functional intasome. Two inner monomers are catalytically active while the CCDs of the two outer monomers appear to play only structural roles. The NED, NTD, and CTD of the outer monomers are disordered in intasome structures. Truncation mutants reveal that integration to a supercoiled plasmid increases without the outer monomer CTDs present. Deletion of the outer CTDs enhances the lifetime of the intasome compared to full length (FL) IN or deletion of the outer monomer NTDs. High ionic strength buffer or several additives, particularly protocatechuic acid (PCA), enhance the integration of FL intasomes by preventing aggregation. These data confirm previous studies suggesting the disordered outer domains of PFV intasomes are not required for intasome assembly or integration. Instead, the outer CTDs contribute to aggregation of PFV intasomes which may be inhibited by high ionic strength buffer or the small molecule PCA.

Details

Language :
English
ISSN :
2045-2322
Volume :
9
Issue :
1
Database :
MEDLINE
Journal :
Scientific reports
Publication Type :
Academic Journal
Accession number :
30644416
Full Text :
https://doi.org/10.1038/s41598-018-36725-1