Mechanism of capsid maturation in a double-stranded DNA virus.
Folding mechanisms of proteins incorporated within supramolecular assemblies, including viruses, are little understood and may differ fundamentally from folding mechanisms of small globular proteins. We describe a novel Raman dynamic probe of hydrogen-isotope exchange to investigate directly these protein folding/assembly pathways. The method is applied to subunit folding in assembly intermediates of the double-stranded DNA bacteriophage P22. The icosahedral procapsid-to-capsid maturation (shell expansion) of P22 is shown to be accompanied by a large increase in exchange protection of peptide beta-strands. The molecular mechanism of shell expansion involves unfolding of metastable tertiary structure to form more stable quaternary contacts and is governed by a surprisingly high activation energy. The results demonstrate that coat subunit folding and capsid expansion are strongly coupled processes. Subunit structure in the procapsid represents a late intermediate along the folding/assembly pathway to the mature capsid. Coupling of folding and assembly is proposed as a general pathway for the construction of supramolecular complexes.
Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri, Kansas City, MO 64110-2499, USA.
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Tuma
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Prevelige
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Thomas
D017100:Bacteriophage P22 / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism*; D055592:Biophysical Phenomena; D001703:Biophysics; D002213:Capsid / Q000737:chemistry* / Q000378:metabolism*; D003545:Cysteine / Q000737:chemistry; D046911:Macromolecular Substances; D011487:Protein Conformation; D017510:Protein Folding; D013059:Spectrum Analysis, Raman; D013816:Thermodynamics; D014364:Tryptophan / Q000737:chemistry
D046911:Macromolecular Substances; D014364:Tryptophan; D003545:Cysteine