期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：17
页码：9885-9890
DOI：10.1073/pnas.95.17.9885
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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.
