5doe
From Proteopedia
Crystal structure of the Human Cytomegalovirus UL53 (residues 72-292)
Structural highlights
Function[UL53_HCMVA] Plays a major role in virion nuclear egress, the first step of virion release from infected cell. Viral capsids are initially assembled within the nucleus, UL53/UL50 complex induces capsids budding and envelopment into the perinuclear space. Then UL53/UL50 complex promotes fusion of perinuclear virion envelope with the outer nuclear membrane, releasing viral capsid into the cytoplasm where it will engages budding sites in the Golgi or trans-Golgi network (By similarity). Publication Abstract from PubMedHerpesvirus 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 A resolution, contained unexpected features including a Bergerat fold resembling that found in certain nucleotide-binding proteins, and a Cys3His 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 A 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. Unexpected features and mechanism of heterodimer formation of a herpesvirus nuclear egress complex.,Lye MF, Sharma M, El Omari K, Filman DJ, Schuermann JP, Hogle JM, Coen DM EMBO J. 2015 Oct 28. pii: e201592651. PMID:26511021[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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