5A3G

Structure of herpesvirus nuclear egress complex subunit M50

5A3G の概要

• エントリーDOI: 10.2210/pdb5a3g/pdb
• NMR情報: BMRB: 26580
• 分子名称: M50 (1 entity in total)
• 機能のキーワード: viral protein, nuclear egress
• 由来する生物種: MURID HERPESVIRUS 1 (MURINE CYTOMEGALOVIRUS)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19402.28

構造登録者

Leigh, K.E.,Boeszoermenyi, A.,Mansueto, M.S.,Sharma, M.,Filman, D.J.,Coen, D.M.,Wagner, G.,Hogle, J.M.,Arthanari, H. (登録日: 2015-06-01, 公開日: 2015-07-15, 最終更新日: 2024-06-19)

主引用文献

Leigh, K.E.,Sharma, M.,Mansueto, M.S.,Boeszoermenyi, A.,Filman, D.J.,Hogle, J.M.,Wagner, G.,Coen, D.M.,Arthanari, H.
Structure of a Herpesvirus Nuclear Egress Complex Subunit Reveals an Interaction Groove that is Essential for Viral Replication
Proc.Natl.Acad.Sci.USA, 112:9010-, 2015

PubMed Abstract: Herpesviruses require a nuclear egress complex (NEC) for efficient transit of nucleocapsids from the nucleus to the cytoplasm. The NEC orchestrates multiple steps during herpesvirus nuclear egress, including disruption of nuclear lamina and particle budding through the inner nuclear membrane. In the important human pathogen human cytomegalovirus (HCMV), this complex consists of nuclear membrane protein UL50, and nucleoplasmic protein UL53, which is recruited to the nuclear membrane through its interaction with UL50. Here, we present an NMR-determined solution-state structure of the murine CMV homolog of UL50 (M50; residues 1-168) with a strikingly intricate protein fold that is matched by no other known protein folds in its entirety. Using NMR methods, we mapped the interaction of M50 with a highly conserved UL53-derived peptide, corresponding to a segment that is required for heterodimerization. The UL53 peptide binding site mapped onto an M50 surface groove, which harbors a large cavity. Point mutations of UL50 residues corresponding to surface residues in the characterized M50 heterodimerization interface substantially decreased UL50-UL53 binding in vitro, eliminated UL50-UL53 colocalization, prevented disruption of nuclear lamina, and halted productive virus replication in HCMV-infected cells. Our results provide detailed structural information on a key protein-protein interaction involved in nuclear egress and suggest that NEC subunit interactions can be an attractive drug target.

PubMed: 26150520
DOI: 10.1073/PNAS.1511140112

実験手法

SOLUTION NMR