Fast closure of N-terminal long loops but slow formation of β strands precedes the folding transition state of Escherichia coli adenylate kinase

Tomer OreviElisha Haas


The nature of the earliest steps of the initiation of the folding pathway of globular proteins is still controversial. To elucidate the role of early closure of long loop structures in the folding transition, we studied the folding kinetics of subdomain structures in Escherichia coli adenylate kinase (AK) using Förster type resonance excitation energy transfer (FRET)-based methods. The overall folding rate of the AK molecule and of several segments that form native β strands is 0.5 ± 0.3 s(-1), in sharp contrast to the 1000-fold faster closure of three long loop structures in the CORE domain. A FRET-based "double kinetics" analysis revealed complex transient changes in the initially closed N-terminal loop structure that then opens and closes again at the end of the folding pathway. The study of subdomain folding in situ suggests a hierarchic ordered folding mechanism, in which early and rapid cross-linking by hydrophobic loop closure provides structural stabilization at the initiation of the folding pathway.


Jan 1, 1992·Annual Review of Biophysics and Biomolecular Structure·S W Englander, L Mayne
Nov 14, 1986·Science·J F Leszczynski, G D Rose
Jun 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·S C Harrison, R Durbin
Jan 23, 1973·Biochemical and Biophysical Research Communications·S S Ristow, D B Wetlaufer
Aug 1, 1995·Proteins·S Govindarajan, R A Goldstein
Mar 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·K A DillH S Chan
Mar 31, 1999·Trends in Biochemical Sciences·R L Baldwin, G D Rose
Apr 14, 1999·Nature Structural Biology·R M Ionescu, C R Matthews
Aug 15, 2000·Annual Review of Biophysics and Biomolecular Structure·W A EatonJ Hofrichter
Jan 9, 2003·Trends in Biochemical Sciences·Valerie Daggett, Alan R Fersht
May 28, 2003·Journal of Molecular Biology·Thomas R Weikl, Ken A Dill
Apr 21, 2004·Nature Structural & Molecular Biology·Kresten Lindorff-LarsenChristopher M Dobson
Jul 1, 2005·Protein Science : a Publication of the Protein Society·Daisuke Kihara
Sep 2, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ying WuOsman Bilsel
Apr 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Wenbing HuS Walter Englander

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