8QXW

HCMV DNA polymerase processivity factor UL44 unphosphorylated NLS 410-433 bound to mouse importin alpha 2

Summary for 8QXW

• Entry DOI: 10.2210/pdb8qxw/pdb
• Descriptor: Importin subunit alpha-1, DNA polymerase processivity factor (3 entities in total)
• Functional Keywords: importin, karyopherin, nuclear, nls, transport protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 2
• Total formula weight: 58005.43

Authors

Cross, E.M.,Marin, O.,Ariawan, D.,Aragao, D.,Cozza, G.,Di Iorio, E.,Forwood, J.K.,Alvisi, G. (deposition date: 2023-10-25, release date: 2023-11-08, Last modification date: 2024-02-07)

Primary citation

Cross, E.M.,Marin, O.,Ariawan, D.,Aragao, D.,Cozza, G.,Di Iorio, E.,Forwood, J.K.,Alvisi, G.
Structural determinants of phosphorylation-dependent nuclear transport of HCMV DNA polymerase processivity factor UL44.
Febs Lett., 598:199-209, 2024

PubMed Abstract: Human cytomegalovirus DNA polymerase processivity factor UL44 is transported into the nucleus by importin (IMP) α/β through a classical nuclear localization signal (NLS), and this region is susceptible to cdc2-mediated phosphorylation at position T427. Whilst phosphorylation within and close to the UL44 NLS regulates nuclear transport, the details remain elusive, due to the paucity of structural information regarding the role of negatively charged cargo phosphate groups. We addressed this issue by studying the effect of UL44 T427 phosphorylation on interaction with several IMPα isoforms by biochemical and structural approaches. Phosphorylation decreased UL44/IMPα affinity 10-fold, and a comparative structural analysis of UL44 NLS phosphorylated and non-phosphorylated peptides complexed with mouse IMPα2 revealed the structural rearrangements responsible for phosphorylation-dependent inhibition of UL44 nuclear import.

PubMed: 38158756
DOI: 10.1002/1873-3468.14797

Experimental method

X-RAY DIFFRACTION (2 Å)