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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2008-2-14
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pubmed:abstractText |
Kinetic partitioning is predicted to be a general mechanism for proteins to fold into their well defined native three-dimensional structure from unfolded states following multiple folding pathways. However, experimental evidence supporting this mechanism is still limited. By using single-molecule atomic force microscopy, here we report experimental evidence supporting the kinetic partitioning mechanism for mechanical unfolding of T4 lysozyme, a small protein composed of two subdomains. We observed that on stretching from its N and C termini, T4 lysozyme unfolds by multiple distinct unfolding pathways: the majority of T4 lysozymes unfold in an all-or-none fashion by overcoming a dominant unfolding kinetic barrier; and a small fraction of T4 lysozymes unfold in three-state fashion involving unfolding intermediate states. The three-state unfolding pathways do not follow well defined routes, instead they display variability and diversity in individual unfolding pathways. The unfolding intermediate states are local energy minima along the mechanical unfolding pathways and are likely to result from the residual structures present in the two subdomains after crossing the main unfolding barrier. These results provide direct evidence for the kinetic partitioning of the mechanical unfolding pathways of T4 lysozyme, and the complex unfolding behaviors reflect the stochastic nature of kinetic barrier rupture in mechanical unfolding processes. Our results demonstrate that single-molecule atomic force microscopy is an ideal tool to investigate the folding/unfolding dynamics of complex multimodule proteins that are otherwise difficult to study using traditional methods.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-10097099,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-10500301,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-10504722,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-10542101,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-10545167,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-10573426,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-10618384,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-10860990,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-10871884,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-12649482,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-12654269,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-12833152,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-14718927,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-14756565,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-15017000,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-15123816,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-15531635,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-15588828,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-15794634,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-15824314,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-1591236,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-16345105,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-16671129,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-16908850,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-17082195,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-17097105,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-17109883,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-17400925,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-17400926,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-17438300,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-17517616,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-2234094,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-2653428,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-3277175,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-3586019,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-6362723,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-7568066,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-7710478,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-8241117,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-8566545,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-8784352,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-9148804,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-9348663,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-9406552,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18272500-9514264
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1091-6490
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
12
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pubmed:volume |
105
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1885-90
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
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pubmed:year |
2008
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pubmed:articleTitle |
Atomic force microscopy reveals parallel mechanical unfolding pathways of T4 lysozyme: evidence for a kinetic partitioning mechanism.
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pubmed:affiliation |
Department of Chemistry, University of British Columbia, Vancouver, BC, Canada V6T 1Z1.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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