Virus maturation: dynamics and mechanism of a stabilizing structural transition that leads to infectivity.
For many viruses, the final stage of assembly involves structural transitions that convert an innocuous precursor particle into an infectious agent. This process -- maturation -- is controlled by proteases that trigger large-scale conformational changes. In this context, protease inhibitor antiviral drugs act by blocking maturation. Recent work has succeeded in determining the folds of representative examples of the five major proteins -- major capsid protein, scaffolding protein, portal, protease and accessory protein -- that are typically involved in capsid assembly. These data provide a framework for detailed mechanistic investigations and elucidation of mutations that affect assembly in various ways. The nature of the conformational change has been elucidated: it entails rigid-body rotations and translations of the arrayed subunits that transfer the interactions between them to different molecular surfaces, accompanied by refolding and redeployment of local motifs. Moreover, it has been possible to visualize maturation at the submolecular level in movies based on time-resolved cryo-electron microscopy.
Steven
Alasdair C
AC
Laboratory of Structural Biology Research, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA. alasdair_steven@nih.gov
Heymann
J Bernard
JB
Cheng
Naiqian
N
Trus
Benes L
BL
Conway
James F
JF
D000818:Animals; D036022:Capsid Proteins / Q000737:chemistry; D003198:Computer Simulation; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000737:chemistry*; D014775:Virus Activation; D019065:Virus Assembly; D014777:Virus Diseases / Q000821:virology*; D014779:Virus Replication; D014780:Viruses / Q000737:chemistry* / Q000254:growth & development*
D036022:Capsid Proteins; D014764:Viral Proteins