Structural basis of membrane budding by the nuclear egress complex of herpesviruses

Bigalke, Janna M.; Heldwein, Ekaterina E.

doi:10.15252/embj.201592359

Structural basis of membrane budding by the nuclear egress complex of herpesviruses

Journal Article · Wed Oct 28 00:00:00 EDT 2015 · EMBO Journal

DOI:https://doi.org/10.15252/embj.201592359· OSTI ID:1547119

Bigalke, Janna M. ^[1]; Heldwein, Ekaterina E. ^[1]

Department of Molecular Biology and Microbiology Tufts University School of Medicine Boston MA USA

Abstract

During nuclear egress, herpesvirus capsids bud at the inner nuclear membrane forming perinuclear viral particles that subsequently fuse with the outer nuclear membrane, releasing capsids into the cytoplasm. This unusual budding process is mediated by the nuclear egress complex ( NEC ) composed of two conserved viral proteins, UL 31 and UL 34. Earlier, we discovered that the herpesvirus nuclear egress complex ( NEC ) could bud synthetic membranes in vitro without the help of other proteins by forming a coat‐like hexagonal scaffold inside the budding membrane. To understand the structural basis of NEC ‐mediated membrane budding, we determined the crystal structures of the NEC from two herpesviruses. The hexagonal lattice observed in the NEC crystals recapitulates the honeycomb coats within the budded vesicles. Perturbation of the oligomeric interfaces through mutagenesis blocks budding in vitro confirming that NEC oligomerization into a honeycomb lattice drives budding. The structure represents the first atomic‐level view of an oligomeric array formed by a membrane‐deforming protein, making possible the dissection of its unique budding mechanism and the design of inhibitors to block it.

View Accepted Manuscript (Publisher)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-06CH11357; AC02-98CH10886

OSTI ID:: 1547119

Alternate ID(s):: OSTI ID: 1228112

Journal Information:: EMBO Journal, Journal Name: EMBO Journal Journal Issue: 23 Vol. 34; ISSN 0261-4189

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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