Insights into Minor Group Rhinovirus Uncoating: The X-ray Structure of the HRV2 Empty Capsid

PLoS Pathogens

José R. Castón¹  Daniel Luque¹  Angela Pickl-Herk²  Jürgen Wruss²  Dieter Blaas²  Damià Garriga³  Núria Verdaguer³ 

[1] Centro Nacional de Biotecnología (CSIC), Cantoblanco, Madrid, Spain;Department of Medical Biochemistry, Max F. Perutz Laboratories, Vienna Biocenter, Medical University of Vienna, Vienna, Austria;Institut de Biologia Molecular de Barcelona (CSIC), Parc Científic de Barcelona, Barcelona, Spain

关键词: Viral packaging;    Viral structure;    Virions;    Crystal structure;    Rhinovirus;    Electron cryo-microscopy;    Electron density;    Protein structure;   

DOI  :  10.1371/journal.ppat.1002473

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Upon attachment to their respective receptor, human rhinoviruses (HRVs) are internalized into the host cell via different pathways but undergo similar structural changes. This ultimately results in the delivery of the viral RNA into the cytoplasm for replication. To improve our understanding of the conformational modifications associated with the release of the viral genome, we have determined the X-ray structure at 3.0 Å resolution of the end-stage of HRV2 uncoating, the empty capsid. The structure shows important conformational changes in the capsid protomer. In particular, a hinge movement around the hydrophobic pocket of VP1 allows a coordinated shift of VP2 and VP3. This overall displacement forces a reorganization of the inter-protomer interfaces, resulting in a particle expansion and in the opening of new channels in the capsid core. These new breaches in the capsid, opening one at the base of the canyon and the second at the particle two-fold axes, might act as gates for the externalization of the VP1 N-terminus and the extrusion of the viral RNA, respectively. The structural comparison between native and empty HRV2 particles unveils a number of pH-sensitive amino acid residues, conserved in rhinoviruses, which participate in the structural rearrangements involved in the uncoating process.

【 授权许可】

CC BY