An experimentally determined protein folding energy landscape

Proceedings of the National Academy of Sciences of the United States of America
Cecilia C Mello, Doug Barrick

Abstract

Energy landscapes have been used to conceptually describe and model protein folding but have been difficult to measure experimentally, in large part because of the myriad of partly folded protein conformations that cannot be isolated and thermodynamically characterized. Here we experimentally determine a detailed energy landscape for protein folding. We generated a series of overlapping constructs containing subsets of the seven ankyrin repeats of the Drosophila Notch receptor, a protein domain whose linear arrangement of modular structural units can be fragmented without disrupting structure. To a good approximation, stabilities of each construct can be described as a sum of energy terms associated with each repeat. The magnitude of each energy term indicates that each repeat is intrinsically unstable but is strongly stabilized by interactions with its nearest neighbors. These linear energy terms define an equilibrium free energy landscape, which shows an early free energy barrier and suggests preferred low-energy routes for folding.

References

Jul 14, 1995·Science·Y BaiS W Englander
Jan 1, 1993·Annual Review of Biochemistry·C R Matthews
Jan 1, 1997·Nature Structural Biology·K A Dill, H S Chan
Jan 26, 1999·Journal of Molecular Biology·K S TangL S Itzhaki
Dec 14, 1999·Nature Structural Biology·M LlinásS Marqusee
Apr 7, 2000·Advances in Protein Chemistry·J N OnuchicN D Socci
Jun 14, 2000·Journal of Molecular Biology·B Zhang, Z y Peng
Jun 25, 2002·Journal of Molecular Biology·Leila K MosaviZheng-yu Peng Zy
Dec 4, 2002·Proceedings of the National Academy of Sciences of the United States of America·Leila K MosaviZheng-Yu Peng
May 10, 2003·Structure·Ewan R G MainLynne Regan
Jun 26, 2003·Protein Science : a Publication of the Protein Society·Cecilia C Mello, Doug Barrick
Oct 24, 2003·Protein Science : a Publication of the Protein Society·Mark E ZweifelDoug Barrick
Jan 1, 1997·Methods in Enzymology·E A Merritt, D J Bacon

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Citations

Oct 23, 2009·Biochemistry·Kan XiongSanford A Asher
Jan 9, 2010·Biochemistry·Diego U Ferreiro, Elizabeth A Komives
Feb 18, 2012·Chemical Reviews·Sulayman A OladepoIgor K Lednev
Apr 10, 2008·Journal of the American Chemical Society·Katherine W Tripp, Doug Barrick
Mar 31, 2011·Journal of the American Chemical Society·Jean-Baptiste RougetCatherine A Royer
Aug 23, 2011·Physical Chemistry Chemical Physics : PCCP·Jan-Hendrik PrinzFrank Noé
Feb 29, 2008·Proceedings of the National Academy of Sciences of the United States of America·Christian LöwJochen Balbach
Jul 18, 2008·Proceedings of the National Academy of Sciences of the United States of America·Diego U Ferreiro, Peter G Wolynes
Nov 6, 2009·Proceedings of the National Academy of Sciences of the United States of America·Frank NoéThomas R Weikl
Aug 10, 2011·Proceedings of the National Academy of Sciences of the United States of America·Mohammed AlQuraishi, Harley H McAdams
May 29, 2012·Proceedings of the National Academy of Sciences of the United States of America·Lauren L Porter, George D Rose
Feb 6, 2013·Proceedings of the National Academy of Sciences of the United States of America·Kevin C JonesAndrei Tokmakoff
Nov 18, 2009·Journal of Biomolecular Structure & Dynamics·P Sklenovsý, M Otyepka
Jun 25, 2008·Annual Review of Biophysics·Ken A DillThomas R Weikl
May 14, 2009·HFSP Journal·Amit MorYaakov Levy
May 10, 2011·The Journal of Chemical Physics·Jan-Hendrik PrinzFrank Noé
Nov 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·George D RoseAmos Maritan
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Timothy O StreetDoug Barrick
May 8, 2007·Proceedings of the National Academy of Sciences of the United States of America·Nicolas D Werbeck, Laura S Itzhaki
May 8, 2007·Proceedings of the National Academy of Sciences of the United States of America·Diego U Ferreiro, Elizabeth A Komives
Apr 13, 2005·Proceedings of the National Academy of Sciences of the United States of America·Ewan R G MainLynne Regan
Feb 15, 2007·Proceedings of the National Academy of Sciences of the United States of America·Alan R Lowe, Laura S Itzhaki
Apr 23, 2015·Proceedings of the National Academy of Sciences of the United States of America·Thuy Phuong DaoDoug Barrick
Jul 9, 2013·Current Opinion in Structural Biology·Yalda Javadi, Laura S Itzhaki
Oct 18, 2011·Journal of Molecular Biology·Andrea Gayle Allgood, Doug Barrick
Jul 27, 2010·Journal of Molecular Biology·Svava K WetzelOliver Zerbe
Aug 4, 2009·Computational Biology and Chemistry·L KapsokalivasK Steinhöfel
Sep 17, 2008·Journal of Molecular Biology·Ellen Kloss, Doug Barrick
Jul 23, 2008·Journal of Molecular Biology·Aitziber L CortajarenaGilad Haran
Feb 5, 2008·Current Opinion in Structural Biology·Doug BarrickElizabeth A Komives
Jan 1, 2008·Journal of Molecular Biology·Svava K WetzelAndreas Plückthun
Dec 19, 2006·Journal of Molecular Biology·Diego U FerreiroElizabeth A Komives
Apr 2, 2005·Protein Science : a Publication of the Protein Society·Olga Y LubmanSergey Korolev
Jul 14, 2009·Protein Science : a Publication of the Protein Society·Ellen Kloss, Doug Barrick
Mar 24, 2007·Proteins·E Prabhu RamanDmitri K Klimov
Jan 30, 2009·Protein Science : a Publication of the Protein Society·Timothy O Street, Doug Barrick
Dec 25, 2007·Protein Science : a Publication of the Protein Society·Naomi Courtemanche, Doug Barrick

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