6T3Z

Crystal structure of the truncated EBV BFRF1-BFLF2 nuclear egress complex

Summary for 6T3Z

• Entry DOI: 10.2210/pdb6t3z/pdb
• Descriptor: Nuclear egress protein 2,Nuclear egress protein 1, MALONATE ION (3 entities in total)
• Functional Keywords: nuclear egress complex, epstein-barr virus, gamma-herpesviral core nec, viral protein
• Biological source: Epstein-Barr virus (strain GD1) (HHV-4); More
• Total number of polymer chains: 1
• Total formula weight: 26069.81

Authors

Muller, Y.A. (deposition date: 2019-10-11, release date: 2020-02-12, Last modification date: 2024-01-24)

Primary citation

Muller, Y.A.,Hage, S.,Alkhashrom, S.,Hollriegl, T.,Weigert, S.,Dolles, S.,Hof, K.,Walzer, S.A.,Egerer-Sieber, C.,Conrad, M.,Holst, S.,Losing, J.,Sonntag, E.,Sticht, H.,Eichler, J.,Marschall, M.
High-resolution crystal structures of two prototypical beta- and gamma-herpesviral nuclear egress complexes unravel the determinants of subfamily specificity.
J.Biol.Chem., 295:3189-3201, 2020

PubMed Abstract: Herpesviruses uniquely express two essential nuclear egress-regulating proteins forming a heterodimeric basic structure of the nuclear egress complex (core NEC). These core NECs serve as a hexameric lattice-structured platform for capsid docking and recruit viral and cellular NEC-associated factors that jointly exert nuclear lamina- and membrane-rearranging functions (multicomponent NEC). Here, we report the X-ray structures of β- and γ-herpesvirus core NECs obtained through an innovative recombinant expression strategy based on NEC-hook::NEC-groove protein fusion constructs. This approach yielded the first structure of γ-herpesviral core NEC, namely the 1.56 Å structure of Epstein-Barr virus (EBV) BFRF1-BFLF2, as well as an increased resolution 1.48 Å structure of human cytomegalovirus (HCMV) pUL50-pUL53. Detailed analysis of these structures revealed that the prominent hook segment is absolutely required for core NEC formation and contributes approximately 80% of the interaction surface of the globular domains of NEC proteins. Moreover, using HCMV::EBV hook domain swap constructs, computational prediction of the roles of individual hook residues for binding, and quantitative binding assays with synthetic peptides presenting the HCMV- and EBV-specific NEC hook sequences, we characterized the unique hook-into-groove NEC interaction at various levels. Although the overall physicochemical characteristics of the protein interfaces differ considerably in these β- and γ-herpesvirus NECs, the binding free energy contributions of residues displayed from identical positions are similar. In summary, the results of our study reveal critical details of the molecular mechanism of herpesviral NEC interactions and highlight their potential as an antiviral drug target.

PubMed: 31980459
DOI: 10.1074/jbc.RA119.011546

Experimental method

X-RAY DIFFRACTION (1.55862788727 Å)