5apm

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

spinqualitylabelsall models 5apm, resolution 4.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5apm is a 3 chain structure with sequence from Human parechovirus 3. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The poorly studied picornavirus, human parechovirus 3 (HPeV3) causes neonatal sepsis with no therapies available. Our 4.3-A resolution structure of HPeV3 on its own and at 15 A 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. Multiple capsid-stabilizing interactions revealed in a high-resolution structure of an emerging picornavirus causing neonatal sepsis.,Shakeel S, Westerhuis BM, Domanska A, Koning RI, Matadeen R, Koster AJ, Bakker AQ, Beaumont T, Wolthers KC, Butcher SJ Nat Commun. 2016 Jul 20;7:11387. doi: 10.1038/ncomms11387. PMID:27435188 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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