7PAB

Varicella zoster Orf24-Orf27 nuclear egress complex

Summary for 7PAB

• Entry DOI: 10.2210/pdb7pab/pdb
• Descriptor: Nuclear egress protein 2,Nuclear egress protein 1, SULFATE ION, ZINC ION, ... (4 entities in total)
• Functional Keywords: vzv, varicella zoster virus, orf24, orf27, orf24-orf27, herpesvirus, nuclear egress, nuclear egress complex, nec, viral protein
• Biological source: Human herpesvirus 3 (HHV-3, Varicella-zoster virus); More
• Total number of polymer chains: 2
• Total formula weight: 100187.69

Authors

Schweininger, J.,Muller, Y.A. (deposition date: 2021-07-29, release date: 2022-01-19, Last modification date: 2024-01-31)

Primary citation

Schweininger, J.,Kriegel, M.,Hage, S.,Conrad, M.,Alkhashrom, S.,Losing, J.,Weiler, S.,Tillmanns, J.,Egerer-Sieber, C.,Decker, A.,Lenac Rovis, T.,Eichler, J.,Sticht, H.,Marschall, M.,Muller, Y.A.
The crystal structure of the varicella-zoster Orf24-Orf27 nuclear egress complex spotlights multiple determinants of herpesvirus subfamily specificity.
J.Biol.Chem., 298:101625-101625, 2022

PubMed Abstract: Varicella-zoster virus (VZV) is a human pathogen from the α-subfamily of herpesviruses. The VZV Orf24-Orf27 complex represents the essential viral core nuclear egress complex (NEC) that orchestrates the egress of the preassembled virus capsids from the nucleus. While previous studies have primarily emphasized that the architecture of core NEC complexes is highly conserved among herpesviruses, the present report focuses on subfamily-specific structural and functional features that help explain the differences in the autologous versus nonautologous interaction patterns observed for NEC formation across herpesviruses. Here, we describe the crystal structure of the Orf24-Orf27 complex at 2.1 Å resolution. Coimmunoprecipitation and confocal imaging data show that Orf24-Orf27 complex formation displays some promiscuity in a herpesvirus subfamily-restricted manner. At the same time, analysis of thermodynamic parameters of NEC formation of three prototypical α-, β-, and γ herpesviruses, i.e., VZV, human cytomegalovirus (HCMV), and Epstein-Barr virus (EBV), revealed highly similar binding affinities for the autologous interaction with specific differences in enthalpy and entropy. Computational alanine scanning, structural comparisons, and mutational data highlight intermolecular interactions shared among α-herpesviruses that are clearly distinct from those seen in β- and γ-herpesviruses, including a salt bridge formed between Orf24-Arg167 and Orf27-Asp126. This interaction is located outside of the hook-into-groove interface and contributes significantly to the free energy of complex formation. Combined, these data explain distinct properties of specificity and permissivity so far observed in herpesviral NEC interactions. These findings will prove valuable in attempting to target multiple herpesvirus core NECs with selective or broad-acting drug candidates.

PubMed: 35074430
DOI: 10.1016/j.jbc.2022.101625

Experimental method

X-RAY DIFFRACTION (2.1 Å)