@article {2034,
	title = {Single molecule force spectroscopy reveals engineered metal chelation is a general approach to enhance mechanical stability of proteins},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	volume = {105},
	number = {32},
	year = {2008},
	note = {ISI Document Delivery No.: 339EKTimes Cited: 16Cited Reference Count: 44Cao, Yi Yoo, Teri Li, Hongbin},
	month = {Aug},
	pages = {11152-11157},
	type = {Article},
	abstract = {Significant mechanical stability is an essential feature shared by many elastomeric proteins, which function as molecular springs in a wide variety of biological machinery and biomaterials of superb mechanical properties. Despite the progress in understanding molecular determinants of mechanical stability, it remains challenging to rationally enhance the mechanical stability of proteins. Using single molecule force spectroscopy and protein engineering techniques, we demonstrate that engineered bi-histidine metal chelation can enhance the mechanical stability of proteins significantly and reversibly. Based on simple thermodynamic cycle analysis, we engineered a bi-histidine metal chelation site into various locations of the small protein, GB1, to achieve preferential stabilization of the native state over the mechanical unfolding transition state of GB1 through the binding of metal ions. Our results demonstrate that the metal chelation can enhance the mechanical stability of GB1 by as much as 100 pN. Since bi-histidine metal chelation sites can be easily implemented, engineered metal chelation provides a general methodology to enhance the mechanical stability of a wide variety of proteins. This general approach in protein mechanics will enable the rational tuning of the mechanical stability of proteins. It will not only open new avenues toward engineering proteins of tailored nanomechanical properties, but also provide new approaches to systematically map the mechanical unfolding pathway of proteins.},
	keywords = {BINDING SITES, charge, DESIGN, DOMAINS, ELASTICITY, engineering, EXTRACELLULAR-MATRIX PROTEIN, mechanical unfolding, PROTEIN, protein mechanics, rational design, SIMULATIONS, STABILIZATION, STRENGTH, THERMOSTABILITY, TITIN},
	isbn = {0027-8424},
	url = {<Go to ISI>://000258560700024},
	author = {Cao, Y. and Yoo, T. and Li, H. B.}
}
