Activation of the herpes simplex virus type-1 origin-binding protein (UL9) by heat shock proteins.
Heat shock proteins participate in the initiation of DNA replication of different organisms by facilitating the assembly of initiation complexes. We have examined the effects of human heat shock proteins (Hsp40 and Hsp70) on the interaction of the herpes simplex virus type-1 initiator protein (UL9) with oriS, one of the viral origins of replication. Hsp40 and Hsp70 act substoichiometrically to increase the affinity of UL9 for oriS. The major contributor to this effect is Hsp40. Heat shock proteins also stimulate the ATPase activity of UL9 with oriS and increase opening of the origin. In contrast, heat shock proteins have no effect on the origin-independent activities of UL9 suggesting that their role is not merely in refolding denatured protein. These observations are consistent with a role for heat shock proteins in activating UL9 to efficiently initiate viral origin-dependent DNA replication. The action of heat shock proteins in this capacity is analogous to their role in activating the initiator proteins of other organisms.
Tanguy Le Gac
Nicolas
N
Department of Biochemistry and Molecular Biology, University of Miami School of Medicine, Miami, Florida 33101-6129, USA.
Boehmer
Paul E
PE
D000251:Adenosine Triphosphatases / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D011196:Potassium Permanganate / Q000494:pharmacology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D014764:Viral Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; C494647:DNAJB1 protein, human; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D011994:Recombinant Proteins; D014764:Viral Proteins; D011196:Potassium Permanganate; C064565:UL9 protein, Human herpesvirus 1; D000251:Adenosine Triphosphatases; D004265:DNA Helicases