Till sidans topp

Sidansvarig: Webbredaktion
Sidan uppdaterades: 2012-09-11 15:12

Tipsa en vän
Utskriftsversion

UL52 Primase Interactions… - Göteborgs universitet Till startsida
Webbkarta
Till innehåll Läs mer om hur kakor används på gu.se

UL52 Primase Interactions in the Herpes Simplex Virus 1 Helicase-Primase Are Affected by Antiviral Compounds and Mutations Causing Drug Resistance

Artikel i vetenskaplig tidskrift
Författare Isabella Muylaert
Zhiyuan Zhao
Per Elias
Publicerad i Journal of Biological Chemistry
Volym 289
Nummer/häfte 47
ISSN 0021-9258
Publiceringsår 2014
Publicerad vid Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi
Språk en
Länkar dx.doi.org/10.1074/jbc.M114.609453
Ämnesord ORIGIN-BINDING PROTEIN, DNA-SYNTHESIS, GENE-PRODUCTS, UL8 PROTEIN, ACYCLOVIR, POLYMERASE, MECHANISM, COMPLEX, REPLICATION, SUPERFAMILY, Biochemistry & Molecular Biology, OW ND, 1993, VIROLOGY, V196, P413
Ämneskategorier Klinisk medicin

Sammanfattning

Herpes simplex virus 1 (HSV-1) UL5/8/52 helicase-primase complex is required for DNA unwinding at the replication fork and synthesis of primers during virus replication, and it has become a promising novel target for antiviral therapy. Using molecular cloning, we have identified three separate domains of UL52. Co-immunoprecipitation experiments in extracts from cells transiently expressing HA-tagged UL5, FLAG-UL8, and enhanced GFP-tagged UL52 domains revealed that the N-terminal domain of UL52 primase binds UL5 helicase and the middle domain interacts with the UL8 accessory protein. In addition, an interaction between the single strand DNA-binding protein ICP8 and the UL52 middle domain was observed. The complex between UL5 and UL52 was stabilized by the antiviral compound BAY 54-6322, and mutations providing resistance to the drug obliterate this effect. Our results also suggest a mechanism for accommodating conformational strain resulting from movement of UL5 and UL52 in opposite directions on the lagging strand template, and they identify molecular complexes that can be further examined by structural biology techniques to resolve the mechanism of primer synthesis during herpesvirus replication. Finally, they help to explain the mechanism of action of a novel class of antiviral compounds currently being evaluated in clinical trials.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11
Dela:

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?