5d5n
From Proteopedia
Crystal Structure of the Human Cytomegalovirus pUL50-pUL53 Complex
Structural highlights
FunctionNEC2_HCMVM Plays an essential role in virion nuclear egress, the first step of virion release from infected cell. Within the host nucleus, NEC1 interacts with the newly formed capsid through the vertexes and directs it to the inner nuclear membrane by associating with NEC2. Induces the budding of the capsid at the inner nuclear membrane as well as its envelopment into the perinuclear space. There, the NEC1/NEC2 complex promotes the fusion of the enveloped capsid with the outer nuclear membrane and the subsequent release of the viral capsid into the cytoplasm where it will reach the secondary budding sites in the host Golgi or trans-Golgi network.[HAMAP-Rule:MF_04024] Publication Abstract from PubMedNuclear replication of cytomegalovirus relies on elaborate mechanisms of nucleocytoplasmic egress of viral particles. Hereby, the role of two essential and conserved viral nuclear egress proteins pUL50 and pUL53 is pivotal. pUL50 and pUL53 heterodimerize and form a core nuclear egress complex (NEC), which is anchored to the inner nuclear membrane and provides a scaffold for the assembly of a multimeric viral-cellular NEC. Here, we report the crystal structure of the pUL50-pUL53 heterodimer (amino acids 1-175 and 50-292, respectively) at 2.44 A resolution. Both proteins adopt a globular fold with mixed alpha and beta secondary structure elements. pUL53-specific features include a zinc-binding site and a hook-like N-terminal extension, the latter representing a hallmark element of the pUL50-pUL53 interaction. The hook-like extension (amino acids 60-87) embraces pUL50 and contributes 1390 A2 to the total interface area (1780 A2). The pUL50 structure overall resembles the recently published NMR structure of the murine cytomegalovirus homolog pM50 but reveals a considerable repositioning of the very C-terminal alpha-helix of pUL50 upon pUL53 binding. pUL53 shows structural resemblance with the GHKL domain of bacterial sensory histidine kinases. A close examination of the crystal structure indicates partial assembly of pUL50-pUL53 heterodimers to hexameric ring-like structures possibly providing additional scaffolding opportunities for NEC. Combined, the structural information on pUL50-pUL53 considerably improves our understanding of the mechanism of HCMV nuclear egress. It may also accelerate the validation of the NEC as a unique target for developing a novel type of antiviral drugs and improved options of broad-spectrum antiherpesviral therapy. Crystal Structure of the Human Cytomegalovirus pUL50-pUL53 Core Nuclear Egress Complex Provides Insight into a Unique Assembly Scaffold for Virus-Host Protein Interactions.,Walzer SA, Egerer-Sieber C, Sticht H, Sevvana M, Hohl K, Milbradt J, Muller YA, Marschall M J Biol Chem. 2015 Oct 2. pii: jbc.C115.686527. PMID:26432641[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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