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Title: Kinetic trapping in protein folding
Abstract The founding principles of protein folding introduced by Christian Anfinsen, together with the numerous mechanistic investigations that followed, assume that protein folding is a thermodynamically controlled process. On the other hand, this review underscores the fact that thermodynamic control is far from being the norm in protein folding, as long as one considers an extended chemical-potential landscape encompassing aggregates, in addition to native, unfolded and intermediate states. Here, we highlight the key role of kinetic trapping of the protein native state relative to unfolded, intermediate and, most importantly, aggregated states. We propose that kinetic trapping serves an important role in biology by protecting the bioactive states of a large number of proteins from deleterious aggregation. In the event that undesired aggregates were somehow formed, specialized intracellular disaggregation machines have evolved to convert any aberrant populations back to the native state, thus restoring a fully bioactive and aggregation-protected protein cohort.  more » « less
Award ID(s):
1616459
NSF-PAR ID:
10180458
Author(s) / Creator(s):
; ; ;
Date Published:
Journal Name:
Protein Engineering, Design and Selection
Volume:
32
Issue:
2
ISSN:
1741-0126
Page Range / eLocation ID:
103 to 108
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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