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Unexpected features and mechanism of heterodimer formation of a herpesvirus nuclear egress complex
Author(s) -
Lye Ming F,
Sharma Mayuri,
El Omari Kamel,
Filman David J,
Schuermann Jonathan P,
Hogle James M,
Coen Donald M
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201592651
Subject(s) - biology , zinc finger , transfection , viral replication , nuclear transport , microbiology and biotechnology , nuclear pore , viral protein , mechanism (biology) , dna , virus , computational biology , biophysics , cell nucleus , nucleus , virology , genetics , gene , philosophy , epistemology , transcription factor
Abstract Herpesvirus nucleocapsids escape from the nucleus in a process orchestrated by a highly conserved, viral nuclear egress complex. In human cytomegalovirus, the complex consists of two proteins, UL50 and UL53. We solved structures of versions of UL53 and the complex by X‐ray crystallography. The UL53 structures, determined at 1.93 and 3.0 Å resolution, contained unexpected features including a Bergerat fold resembling that found in certain nucleotide‐binding proteins, and a Cys 3 His zinc finger. Substitutions of zinc‐coordinating residues decreased UL50–UL53 co‐localization in transfected cells, and, when incorporated into the HCMV genome, ablated viral replication. The structure of the complex, determined at 2.47 Å resolution, revealed a mechanism of heterodimerization in which UL50 clamps onto helices of UL53 like a vise. Substitutions of particular residues on the interaction interface disrupted UL50–UL53 co‐localization in transfected cells and abolished virus production. The structures and the identification of contacts can be harnessed toward the rational design of novel and highly specific antiviral drugs and will aid in the detailed understanding of nuclear egress.

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