HCMV gB shares structural and functional properties with gB proteins from other herpesviruses

Sapna Sharma; Todd W. Wisner; David C. Johnson; Ekaterina E. Heldwein

doi:10.1016/j.virol.2012.09.024

HCMV gB shares structural and functional properties with gB proteins from other herpesviruses

Sapna Sharma, Todd W. Wisner, David C. Johnson, Ekaterina E. Heldwein

Molecular Microbiology and Immunology

Research output: Contribution to journal › Article › peer-review

46 Scopus citations

Abstract

Glycoprotein B (gB) facilitates HCMV entry into cells by binding receptors and mediating membrane fusion. The crystal structures of gB ectodomains from HSV-1 and EBV are available, but little is known about the HCMV gB structure. Using multiangle light scattering and electron microscopy, we show here that HCMV gB ectodomain is a trimer with the overall shape similar to HSV-1 and EBV gB ectodomains. HCMV gB ectodomain forms rosettes similar to rosettes formed by EBV gB and the postfusion forms of other viral fusogens. Substitution of several bulky hydrophobic residues within the putative fusion loops with more hydrophilic residues reduced rosette formation and abolished cell fusion. We propose that like gB proteins from HSV-1 and EBV, HCMV gB has two internal hydrophobic fusion loops that likely interact with target membranes. Our work establishes structural and functional similarities between gB proteins from three subfamilies of herpesviruses.

Original language	English (US)
Pages (from-to)	239-249
Number of pages	11
Journal	Virology
Volume	435
Issue number	2
DOIs	https://doi.org/10.1016/j.virol.2012.09.024
State	Published - Jan 20 2013

Keywords

Cytomegalovirus
Entry
Fusion loop
Glycoprotein B
Glycosylation
Herpesvirus
Membrane fusion
Rosette

ASJC Scopus subject areas

Virology

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10.1016/j.virol.2012.09.024

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title = "HCMV gB shares structural and functional properties with gB proteins from other herpesviruses",

abstract = "Glycoprotein B (gB) facilitates HCMV entry into cells by binding receptors and mediating membrane fusion. The crystal structures of gB ectodomains from HSV-1 and EBV are available, but little is known about the HCMV gB structure. Using multiangle light scattering and electron microscopy, we show here that HCMV gB ectodomain is a trimer with the overall shape similar to HSV-1 and EBV gB ectodomains. HCMV gB ectodomain forms rosettes similar to rosettes formed by EBV gB and the postfusion forms of other viral fusogens. Substitution of several bulky hydrophobic residues within the putative fusion loops with more hydrophilic residues reduced rosette formation and abolished cell fusion. We propose that like gB proteins from HSV-1 and EBV, HCMV gB has two internal hydrophobic fusion loops that likely interact with target membranes. Our work establishes structural and functional similarities between gB proteins from three subfamilies of herpesviruses.",

keywords = "Cytomegalovirus, Entry, Fusion loop, Glycoprotein B, Glycosylation, Herpesvirus, Membrane fusion, Rosette",

author = "Sapna Sharma and Wisner, {Todd W.} and Johnson, {David C.} and Heldwein, {Ekaterina E.}",

note = "Funding Information: We thank William Britt (University of Alabama) for providing monoclonal antibodies and hybridomas used in this work, Maria Eriksson at the HMS EM Core Facility for help with sample preparation and data acquisition, Michael Berne at the Tufts University Core Facility for N-terminal protein sequencing and MALDI-TOFF mass spectrometry, Ayman Ismail for help with MALS experiments, Janna Bigalke for MALS data analysis and Fig. 7 , and Motti Hakim at the Weizmann Institute for homology modeling. We also thank Gary Cohen, Roselyn Eisenberg, and Abraham Sonenshein for critical reading of the manuscript. This work was funded by the NIH Grant 1DP20D001996 , by the Pew Scholar Program in Biomedical Sciences , by the CFAR Developmental Research Fund Grant (E.E.H.), and by the NIH Grant R01AI081517 (D.C.J.).",

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AU - Sharma, Sapna

AU - Wisner, Todd W.

AU - Johnson, David C.

AU - Heldwein, Ekaterina E.

N1 - Funding Information: We thank William Britt (University of Alabama) for providing monoclonal antibodies and hybridomas used in this work, Maria Eriksson at the HMS EM Core Facility for help with sample preparation and data acquisition, Michael Berne at the Tufts University Core Facility for N-terminal protein sequencing and MALDI-TOFF mass spectrometry, Ayman Ismail for help with MALS experiments, Janna Bigalke for MALS data analysis and Fig. 7 , and Motti Hakim at the Weizmann Institute for homology modeling. We also thank Gary Cohen, Roselyn Eisenberg, and Abraham Sonenshein for critical reading of the manuscript. This work was funded by the NIH Grant 1DP20D001996 , by the Pew Scholar Program in Biomedical Sciences , by the CFAR Developmental Research Fund Grant (E.E.H.), and by the NIH Grant R01AI081517 (D.C.J.).

PY - 2013/1/20

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N2 - Glycoprotein B (gB) facilitates HCMV entry into cells by binding receptors and mediating membrane fusion. The crystal structures of gB ectodomains from HSV-1 and EBV are available, but little is known about the HCMV gB structure. Using multiangle light scattering and electron microscopy, we show here that HCMV gB ectodomain is a trimer with the overall shape similar to HSV-1 and EBV gB ectodomains. HCMV gB ectodomain forms rosettes similar to rosettes formed by EBV gB and the postfusion forms of other viral fusogens. Substitution of several bulky hydrophobic residues within the putative fusion loops with more hydrophilic residues reduced rosette formation and abolished cell fusion. We propose that like gB proteins from HSV-1 and EBV, HCMV gB has two internal hydrophobic fusion loops that likely interact with target membranes. Our work establishes structural and functional similarities between gB proteins from three subfamilies of herpesviruses.

AB - Glycoprotein B (gB) facilitates HCMV entry into cells by binding receptors and mediating membrane fusion. The crystal structures of gB ectodomains from HSV-1 and EBV are available, but little is known about the HCMV gB structure. Using multiangle light scattering and electron microscopy, we show here that HCMV gB ectodomain is a trimer with the overall shape similar to HSV-1 and EBV gB ectodomains. HCMV gB ectodomain forms rosettes similar to rosettes formed by EBV gB and the postfusion forms of other viral fusogens. Substitution of several bulky hydrophobic residues within the putative fusion loops with more hydrophilic residues reduced rosette formation and abolished cell fusion. We propose that like gB proteins from HSV-1 and EBV, HCMV gB has two internal hydrophobic fusion loops that likely interact with target membranes. Our work establishes structural and functional similarities between gB proteins from three subfamilies of herpesviruses.

KW - Cytomegalovirus

KW - Entry

KW - Fusion loop

KW - Glycoprotein B

KW - Glycosylation

KW - Herpesvirus

KW - Membrane fusion

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ER -

HCMV gB shares structural and functional properties with gB proteins from other herpesviruses

Abstract

Keywords

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