9MIK

Gallid alphaherpesvirus-1 large tegument protein bipartite NLS1 in complex with Importin alpha

Summary for 9MIK

• Entry DOI: 10.2210/pdb9mik/pdb
• Descriptor: Large tegument protein peptide, Importin subunit alpha-1 (3 entities in total)
• Functional Keywords: nuclear import, nuclear localisation signal, large tegument protein, gallid alphaherpesvirus-1, transport protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 2
• Total formula weight: 58162.92

Authors

Nath, B.K.,Swarbrick, C.M.D.,Sarker, S.,Forwood, J.K. (deposition date: 2024-12-12, release date: 2026-02-04)

Primary citation

Nath, B.K.,Swarbrick, C.M.D.,Blades, R.,Ariawan, D.,Tietz, O.,Alvisi, G.,Forwood, J.K.,Sarker, S.
Structural Insights Into the Nuclear Import of Gallid Alphaherpesvirus 1 Large Tegument Protein.
Microbiologyopen, 15:e70216-e70216, 2026

PubMed Abstract: Gallid alphaherpesvirus 1 (GaAHV-1), also referred to as infectious laryngotracheitis virus (ILTV), primarily targets the upper respiratory tract of chickens. This infection leads to significant economic setbacks worldwide in the poultry sector, driven by reductions in egg output, weight gain, and increased mortality rates. Even with the broad implementation of vaccination programs, ILTV outbreaks remain a challenge, as vaccine strains can revert to a virulent form under field conditions. This underscores the need to explore targeted therapeutic options, including a deeper understanding of GaAHV-1's nuclear trafficking mechanisms, critical for viral replication. The herpesvirus large tegument protein UL36 contains N-terminal nuclear localization signals (NLSs) that are essential for capsid routing to the nuclear pore complex (NPC). However, the mechanisms by which UL36 of GaAHV-1 mediates nuclear import remain poorly understood. In this study, we identified the NLS of GaAHV-1 UL36 and elucidated their binding mechanism with human nuclear import proteins. Using high-resolution crystal structures and quantitative assays, we mapped the specific residues and regions within UL36's N-terminal domain that facilitate binding to importin (IMP) α. Moreover, we revealed variations in binding affinities among different importin isoforms. Our biochemical and structural analyses demonstrate that the predicted N-terminal NLS of GaAHV-1 UL36 is critical for IMPα binding. These findings provide detailed molecular insights into the interaction between the GaAHV-1 large tegument protein and IMPs, paving the way for the development of targeted antiviral therapies.

PubMed: 41569631
DOI: 10.1002/mbo3.70216

Experimental method

X-RAY DIFFRACTION (2.6 Å)