TY - JOUR
T1 - Stabilization of a protein conferred by an increase in folded state entropy
AU - Dagan, Shlomi
AU - Hagai, Tzachi
AU - Gavrilov, Yulian
AU - Kapon, Ruti
AU - Levy, Yaakov
AU - Reich, Ziv
N1 - Carolito Stiftung; Kimmelman Center for Biomolecular Structure and Assembly; Israel Science FoundationWe thank Drs. Shira Albeck, Orly Dym, Yoav Peleg, and Tamar Unger (Israel Structural Proteomic Center, Weizmann Institute of Science) for their help in producing the proteins used in this study; Drs. Vlad Brumfeld and Yosef Scholnik for assistance with the CD analyses; and Drs. Amnon Horovitz and Gideon Schreiber for critical discussions and helpful suggestions. This work was supported by the Carolito Stiftung (Z. R.), the Kimmelman Center for Biomolecular Structure and Assembly (Y. L. and Z. R.), and the Israel Science Foundation (Y. L.). Y. L. holds the Lillian and George Lyttle Career Development Chair.
PY - 2013/6/25
Y1 - 2013/6/25
N2 - Entropic stabilization of native protein structures typically relies on strategies that serve to decrease the entropy of the unfolded state. Here we report, using a combination of experimental and computational approaches, on enhanced thermodynamic stability conferred by an increase in the configurational entropy of the folded state. The enhanced stability is observed upon modifications of a loop region in the enzyme acylphosphatase and is achieved despite significant enthalpy losses. The modifications that lead to increased stability, as well as those that result in destabilization, however, strongly compromise enzymatic activity, rationalizing the preservation of the native loop structure even though it does not provide the protein with maximal stability or kinetic foldability.
AB - Entropic stabilization of native protein structures typically relies on strategies that serve to decrease the entropy of the unfolded state. Here we report, using a combination of experimental and computational approaches, on enhanced thermodynamic stability conferred by an increase in the configurational entropy of the folded state. The enhanced stability is observed upon modifications of a loop region in the enzyme acylphosphatase and is achieved despite significant enthalpy losses. The modifications that lead to increased stability, as well as those that result in destabilization, however, strongly compromise enzymatic activity, rationalizing the preservation of the native loop structure even though it does not provide the protein with maximal stability or kinetic foldability.
KW - Loop closure entropy
KW - Molecular dynamics
KW - Protein folding
UR - http://www.scopus.com/inward/record.url?scp=84879525246&partnerID=8YFLogxK
U2 - https://doi.org/10.1073/pnas.1302284110
DO - https://doi.org/10.1073/pnas.1302284110
M3 - مقالة
C2 - 23754389
SN - 0027-8424
VL - 110
SP - 10628
EP - 10633
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 26
ER -