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Title: An unexpected twist in viral capsid maturation

Abstract

Lambda-like double-stranded (ds) DNA bacteriophage undergo massive conformational changes in their capsid shell during the packaging of their viral genomes. Capsid shells are complex organizations of hundreds of protein subunits that assemble into intricate quaternary complexes that ultimately are able to withstand over 50 atm of pressure during genome packaging. The extensive integration between subunits in capsids requires the formation of an intermediate complex, termed a procapsid, from which individual subunits can undergo the necessary refolding and structural rearrangements needed to transition to the more stable capsid. Although various mature capsids have been characterized at atomic resolution, no such procapsid structure is available for a dsDNA virus or bacteriophage. Here we present a procapsid X-ray structure at 3.65 {angstrom} resolution, termed prohead II, of the lambda-like bacteriophage HK97, the mature capsid structure of which was previously solved to 3.44 {angstrom}. A comparison of the two largely different capsid forms has unveiled an unprecedented expansion mechanism that describes the transition. Crystallographic and hydrogen/deuterium exchange data presented here demonstrate that the subunit tertiary structures are significantly different between the two states, with twisting and bending motions occurring in both helical and -sheet regions. We also identified subunit interactions at each three-fold axismore » of the capsid that are maintained throughout maturation. The interactions sustain capsid integrity during subunit refolding and provide a fixed hinge from which subunits undergo rotational and translational motions during maturation. Previously published calorimetric data of a closely related bacteriophage, P22, showed that capsid maturation was an exothermic process that resulted in a release of 90 kJ mol{sup -1} of energy. We propose that the major tertiary changes presented in this study reveal a structural basis for an exothermic maturation process probably present in many dsDNA bacteriophage and possibly viruses such as herpesvirus, which share the HK97 subunit fold.« less

Authors:
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Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1005558
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nature; Journal Volume: 458; Journal Issue: 02, 2009
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; 99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE; BACTERIOPHAGES; BENDING; COMPLEXES; CONFORMATIONAL CHANGES; DATA; DNA; ENERGY; EXPANSION; INTERACTIONS; MATURATION; PACKAGING; PROTEINS; RESOLUTION; SHELLS; VIRUSES

Citation Formats

Gertsman, Ilya, Gan, Lu, Guttman, Miklos, Lee, Kelly, Speir, Jeffrey A., Duda, Robert L., Hendrix, Roger W., Komives, Elizabeth A., Johnson, John E., Pitt), Scripps), and UCSD). An unexpected twist in viral capsid maturation. United States: N. p., 2009. Web. doi:10.1038/nature07686.
Gertsman, Ilya, Gan, Lu, Guttman, Miklos, Lee, Kelly, Speir, Jeffrey A., Duda, Robert L., Hendrix, Roger W., Komives, Elizabeth A., Johnson, John E., Pitt), Scripps), & UCSD). An unexpected twist in viral capsid maturation. United States. doi:10.1038/nature07686.
Gertsman, Ilya, Gan, Lu, Guttman, Miklos, Lee, Kelly, Speir, Jeffrey A., Duda, Robert L., Hendrix, Roger W., Komives, Elizabeth A., Johnson, John E., Pitt), Scripps), and UCSD). Tue . "An unexpected twist in viral capsid maturation". United States. doi:10.1038/nature07686.
@article{osti_1005558,
title = {An unexpected twist in viral capsid maturation},
author = {Gertsman, Ilya and Gan, Lu and Guttman, Miklos and Lee, Kelly and Speir, Jeffrey A. and Duda, Robert L. and Hendrix, Roger W. and Komives, Elizabeth A. and Johnson, John E. and Pitt) and Scripps) and UCSD)},
abstractNote = {Lambda-like double-stranded (ds) DNA bacteriophage undergo massive conformational changes in their capsid shell during the packaging of their viral genomes. Capsid shells are complex organizations of hundreds of protein subunits that assemble into intricate quaternary complexes that ultimately are able to withstand over 50 atm of pressure during genome packaging. The extensive integration between subunits in capsids requires the formation of an intermediate complex, termed a procapsid, from which individual subunits can undergo the necessary refolding and structural rearrangements needed to transition to the more stable capsid. Although various mature capsids have been characterized at atomic resolution, no such procapsid structure is available for a dsDNA virus or bacteriophage. Here we present a procapsid X-ray structure at 3.65 {angstrom} resolution, termed prohead II, of the lambda-like bacteriophage HK97, the mature capsid structure of which was previously solved to 3.44 {angstrom}. A comparison of the two largely different capsid forms has unveiled an unprecedented expansion mechanism that describes the transition. Crystallographic and hydrogen/deuterium exchange data presented here demonstrate that the subunit tertiary structures are significantly different between the two states, with twisting and bending motions occurring in both helical and -sheet regions. We also identified subunit interactions at each three-fold axis of the capsid that are maintained throughout maturation. The interactions sustain capsid integrity during subunit refolding and provide a fixed hinge from which subunits undergo rotational and translational motions during maturation. Previously published calorimetric data of a closely related bacteriophage, P22, showed that capsid maturation was an exothermic process that resulted in a release of 90 kJ mol{sup -1} of energy. We propose that the major tertiary changes presented in this study reveal a structural basis for an exothermic maturation process probably present in many dsDNA bacteriophage and possibly viruses such as herpesvirus, which share the HK97 subunit fold.},
doi = {10.1038/nature07686},
journal = {Nature},
number = 02, 2009,
volume = 458,
place = {United States},
year = {Tue Apr 14 00:00:00 EDT 2009},
month = {Tue Apr 14 00:00:00 EDT 2009}
}