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Protein translocation through a tunnel induces changes in folding kinetics: A lattice model study
Author(s) -
Contreras Martínez Lydia M.,
MartínezVeracoechea Francisco J.,
Pohkarel Prabhas,
Stroock Abraham D.,
Escobedo Fernando A.,
DeLisa Matthew P.
Publication year - 2006
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.20832
Subject(s) - ribosome , protein folding , biophysics , kinetics , folding (dsp implementation) , chemical physics , translocon , crystallography , ribosomal protein , lattice protein , downhill folding , chemistry , physics , phi value analysis , rna , chromosomal translocation , biology , biochemistry , gene , electrical engineering , engineering , quantum mechanics
Compaction of a nascent polypeptide chain inside the ribosomal exit tunnel, before it leaves the ribosome, has been proposed to accelerate the folding of newly synthesized proteins following their release from the ribosome. Thus, we used Kinetic Monte Carlo simulations of a minimalist on‐lattice model to explore the effect that polypeptide translocation through a variety of channels has on protein folding kinetics. Our results demonstrate that tunnel confinement promotes faster folding of a well‐designed protein relative to its folding in free space by displacing the unfolded state towards more compact structures that are closer to the transition state. Since the tunnel only forbids rarely visited, extended configurations, it has little effect on a “poorly designed” protein whose unfolded state is largely composed of low‐energy, compact, misfolded configurations. The beneficial effect of the tunnel depends on its width; for example, a too‐narrow tunnel enforces unfolded states with limited or no access to the transition state, while a too‐wide tunnel has no effect on the unfolded state entropy. We speculate that such effects are likely to play an important role in the folding of some proteins or protein domains in the cellular environment and might dictate whether a protein folds co‐translationally or post‐translationally. © 2006 Wiley Periodicals, Inc.