5APM

Multiple capsid-stabilizing protein-RNA and protein-protein interactions revealed in a high-resolution structure of an emerging picornavirus causing neonatal sepsis

5APM の概要

• エントリーDOI: 10.2210/pdb5apm/pdb
• EMDBエントリー: 3137
• 分子名称: VP1, VP3, VP0 (3 entities in total)
• 機能のキーワード: virus, picornavirus, parechovirus, human parechovirus 3, hpev3, neonatal sepsis, cryoem, image processing, single particle analysis
• 由来する生物種: HUMAN PARECHOVIRUS 3 (HPEV3); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 77999.49

構造登録者

Shakeel, S.,Westerhuis, B.M.,Domanska, A.,Koning, R.I.,Matadeen, R.,Koster, A.J.,Bakker, A.Q.,Beaumont, T.,Wolthers, K.C.,Butcher, S.J. (登録日: 2015-09-17, 公開日: 2016-07-27, 最終更新日: 2024-05-08)

主引用文献

Shakeel, S.,Westerhuis, B.M.,Domanska, A.,Koning, R.I.,Matadeen, R.,Koster, A.J.,Bakker, A.Q.,Beaumont, T.,Wolthers, K.C.,Butcher, S.J.
Multiple Capsid-Stabilizing Interactions Revealed in a High-Resolution Structure of an Emerging Picornavirus Causing Neonatal Sepsis
Nat.Commun., 7:11387-, 2016

PubMed Abstract: The poorly studied picornavirus, human parechovirus 3 (HPeV3) causes neonatal sepsis with no therapies available. Our 4.3-Å resolution structure of HPeV3 on its own and at 15 Å resolution in complex with human monoclonal antibody Fabs demonstrates the expected picornavirus capsid structure with three distinct features. First, 25% of the HPeV3 RNA genome in 60 sites is highly ordered as confirmed by asymmetric reconstruction, and interacts with conserved regions of the capsid proteins VP1 and VP3. Second, the VP0 N terminus stabilizes the capsid inner surface, in contrast to other picornaviruses where on expulsion as VP4, it forms an RNA translocation channel. Last, VP1's hydrophobic pocket, the binding site for the antipicornaviral drug, pleconaril, is blocked and thus inappropriate for antiviral development. Together, these results suggest a direction for development of neutralizing antibodies, antiviral drugs based on targeting the RNA-protein interactions and dissection of virus assembly on the basis of RNA nucleation.

PubMed: 27435188
DOI: 10.1038/NCOMMS11387

実験手法

ELECTRON MICROSCOPY (4.3 Å)