Conformational equilibria and intrinsic affinities define integrin activation.

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

SUBMITTER: Li J 

PROVIDER: S-EPMC5331762 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature