Format

Send to

Choose Destination
Structure. 2014 Feb 4;22(2):230-7. doi: 10.1016/j.str.2013.11.007. Epub 2013 Dec 19.

Architecture of a dsDNA viral capsid in complex with its maturation protease.

Author information

1
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
2
Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.
3
Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences Utrecht University, Padualaan 8, 3584 CH, Utrecht, The Netherlands; Netherlands Proteomics Centre Padualaan 8, 3584CH, Utrecht, The Netherlands.
4
Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: jackj@scripps.edu.

Abstract

Most double-stranded DNA (dsDNA) viruses, including bacteriophages and herpesviruses, rely on a staged assembly process of capsid formation. A viral protease is required for many of them to disconnect scaffolding domains/proteins from the capsid shell, therefore priming the maturation process. We used the bacteriophage HK97 as a model system to decipher the molecular mechanisms underlying the recruitment of the maturation protease by the assembling procapsid and the influence exerted onto the latter. Comparisons of the procapsid with and without protease using single-particle cryoelectron microscopy reconstructions, hydrogen/deuterium exchange coupled to mass spectrometry, and native mass spectrometry demonstrated that the protease interacts with the scaffolding domains within the procapsid interior and stabilizes them as well as the whole particle. The results suggest that the thermodynamic consequences of protease packaging are to shift the equilibrium between isolated coat subunit capsomers and procapsid in favor of the latter by stabilizing the assembled particle before making the process irreversible through proteolysis of the scaffolding domains.

PMID:
24361271
PMCID:
PMC3939775
DOI:
10.1016/j.str.2013.11.007
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center