@article {988991,
	title = {Conformational equilibria and intrinsic affinities define integrin activation},
	journal = {EMBO J},
	year = {2017},
	month = {2017 Jan 25},
	abstract = {We show that the three conformational states of integrin α5β1 have discrete free energies and define activation by measuring intrinsic affinities for ligand of each state and the equilibria linking them. The 5,000-fold higher affinity of the extended-open state than the bent-closed and extended-closed states demonstrates profound regulation of affinity. Free energy requirements for activation are defined with protein fragments and intact α5β1 On the surface of K562 cells, α5β1 is 99.8\% bent-closed. Stabilization of the bent conformation by integrin transmembrane and cytoplasmic domains must be overcome by cellular energy input to stabilize extension. Following extension, headpiece opening is energetically favored. N-glycans and leg domains in each subunit that connect the ligand-binding head to the membrane repel or crowd one another and regulate conformational equilibria in favor of headpiece opening. The results suggest new principles for regulating signaling in the large class of receptors built from extracellular domains in tandem with single-span transmembrane domains.},
	issn = {1460-2075},
	doi = {10.15252/embj.201695803},
	author = {Li, Jing and Su, Yang and Xia, Wei and Qin, Yan and Humphries, Martin J and Vestweber, Dietmar and Caba{\~n}as, Carlos and Lu, Chafen and Springer, Timothy A.}
}
