Two distinct trimeric conformations of natively membrane-anchored full-length herpes simplex virus 1 glycoprotein B.

نویسندگان

  • Tzviya Zeev-Ben-Mordehai
  • Daven Vasishtan
  • Anna Hernández Durán
  • Benjamin Vollmer
  • Paul White
  • Arun Prasad Pandurangan
  • C Alistair Siebert
  • Maya Topf
  • Kay Grünewald
چکیده

Many viruses are enveloped by a lipid bilayer acquired during assembly, which is typically studded with one or two types of glycoproteins. These viral surface proteins act as the primary interface between the virus and the host. Entry of enveloped viruses relies on specialized fusogen proteins to help merge the virus membrane with the host membrane. In the multicomponent herpesvirus fusion machinery, glycoprotein B (gB) acts as this fusogen. Although the structure of the gB ectodomain postfusion conformation has been determined, any other conformations (e.g., prefusion, intermediate conformations) have so far remained elusive, thus restricting efforts to develop antiviral treatments and prophylactic vaccines. Here, we have characterized the full-length herpes simplex virus 1 gB in a native membrane by displaying it on cell-derived vesicles and using electron cryotomography. Alongside the known postfusion conformation, a novel one was identified. Its structure, in the context of the membrane, was determined by subvolume averaging and found to be trimeric like the postfusion conformation, but appeared more condensed. Hierarchical constrained density-fitting of domains unexpectedly revealed the fusion loops in this conformation to be apart and pointing away from the anchoring membrane. This vital observation is a substantial step forward in understanding the complex herpesvirus fusion mechanism, and opens up new opportunities for more targeted intervention of herpesvirus entry.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Construction of an Eukaryotic Expression Vector Encoding Herpes Simplex Virus Type 2 Glycoprotein D and In Vitro Expression of the Desired Protein

To construct of an eukaryotic expression vector encoding herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2), an Iranian isolate of HSV-2 was propagated in HeLa cell line and its DNA was extracted and used as template in polymerase chain reactions (PCR), to amplify gD2 gene. Primers were designed and the restriction enzyme sites for EcoRI and XhoI were considered at their 5′ ends respectiv...

متن کامل

Random linker-insertion mutagenesis to identify functional domains of herpes simplex virus type 1 glycoprotein B.

Herpes simplex virus glycoprotein B (gB) is one of four glycoproteins essential for viral entry and cell fusion. Recently, an x-ray structure of the nearly full-length trimeric gB ectodomain was determined. Five structural domains and two linker regions were identified in what is probably a postfusion conformation. To identify functional domains of gB, we performed random linker-insertion mutag...

متن کامل

Expression of the Herpes Simplex Virus Type 2 Glycoprotein D in Baculovirus Expression System and Evaluation of Its Immunogenicity in Guinea Pigs

Background: Herpes simplex virus type 2 (HSV-2) is highly prevalent and major cause of genital herpes in humans. The life-long nature of infection and the increasing prevalence of genital herpes imply that vaccination is the best strategy for controlling the spread of infection and limiting HSV disease. HSV glycoprotein D (gD) is one of the most important viral immunogen which has an essential ...

متن کامل

Detection of Herpes Simplex Virus Antibodies Using the Whole Virus and Recombinant gD

Background and Aims: Herpes simplex virus type 1 (HSV1) remains a potentially serious health problem world wide. All infected people, including asymptomatic ones, are potential sources for virus transmission. Virus envelope contains at least 13 glycoproteins, which glycoprotein D is the major target of immune responses. The aim of this study was development of a specific method that is a more...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Proceedings of the National Academy of Sciences of the United States of America

دوره 113 15  شماره 

صفحات  -

تاریخ انتشار 2016