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dc.contributor.authorLeigh, Kendra
dc.contributor.authorSharma, Mayuri
dc.contributor.authorMansueto, My Sam
dc.contributor.authorBoeszoermenyi, Andras
dc.contributor.authorFilman, David
dc.contributor.authorHogle, James
dc.contributor.authorWagner, Gerhard
dc.contributor.authorCoen, Donald
dc.contributor.authorArthanari, Haribabu
dc.date.accessioned2019-10-05T03:29:19Z
dc.date.issued2015
dc.identifier.citationLeigh, Kendra E., Mayuri Sharma, My Sam Mansueto, Andras Boeszoermenyi, David J. Filman, James M. Hogle, Gerhard Wagner, Donald M. Coen, and Haribabu Arthanari. 2015. “Structure of a Herpesvirus Nuclear Egress Complex Subunit Reveals an Interaction Groove That Is Essential for Viral Replication.” Proceedings of the National Academy of Sciences 112 (29): 9010–15. https://doi.org/10.1073/pnas.1511140112.
dc.identifier.issn0027-8424
dc.identifier.issn0744-2831
dc.identifier.issn1091-6490
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41483056*
dc.description.abstractHerpesviruses require a nuclear egress complex (NEC) for efficient transit of nucleocapsids from the nucleus to the cytoplasm. The NEC orchestrates multiple steps during herpesvirus nuclear egress, including disruption of nuclear lamina and particle budding through the inner nuclear membrane. In the important human pathogen human cytomegalovirus (HCMV), this complex consists of nuclear membrane protein UL50, and nucleoplasmic protein UL53, which is recruited to the nuclear membrane through its interaction with UL50. Here, we present an NMR-determined solution-state structure of the murine CMV homolog of UL50 (M50; residues 1-168) with a strikingly intricate protein fold that is matched by no other known protein folds in its entirety. Using NMR methods, we mapped the interaction of M50 with a highly conserved UL53-derived peptide, corresponding to a segment that is required for heterodimerization. The UL53 peptide binding site mapped onto an M50 surface groove, which harbors a large cavity. Point mutations of UL50 residues corresponding to surface residues in the characterized M50 heterodimerization interface substantially decreased UL50-UL53 binding in vitro, eliminated UL50-UL53 colocalization, prevented disruption of nuclear lamina, and halted productive virus replication in HCMV-infected cells. Our results provide detailed structural information on a key protein-protein interaction involved in nuclear egress and suggest that NEC subunit interactions can be an attractive drug target.
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dash.licenseLAA
dc.titleStructure of a herpesvirus nuclear egress complex subunit reveals an interaction groove that is essential for viral replication
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalProceedings of the National Academy of Sciences of the United States of America
dash.depositing.authorCoen, Donald Mark::f1d1eb8434c5ee0d3e2fa13c1a313e4d::600
dc.date.available2019-10-05T03:29:19Z
dash.workflow.comments1Science Serial ID 91307
dc.identifier.doi10.1073/pnas.1511140112
dash.source.volume112;29
dash.source.page9010


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