Energy landscape differences among integrins establish the framework for understanding activation. Academic Article uri icon

abstract

  • Why do integrins differ in basal activity, and how does affinity for soluble ligand correlate with cellular adhesiveness? We show that basal conformational equilibrium set points for integrin ?4?1 are cell type specific and differ from integrin ?5?1 when the two integrins are coexpressed on the same cell. Although ?4?1 is easier to activate, its high-affinity state binds vascular cell adhesion molecule and fibronectin 100- to 1,000-fold more weakly than ?5?1 binds fibronectin. Furthermore, the difference in affinity between the high- and low-affinity states is more compressed in ?4?1 (600- to 800-fold) than in ?5?1 (4,000- to 6,000-fold). ?4?1 basal conformational equilibria differ among three cell types, define affinity for soluble ligand and readiness for priming, and may reflect differences in interactions with intracellular adaptors but do not predict cellular adhesiveness for immobilized ligand. The measurements here provide a necessary framework for understanding integrin activation in intact cells, including activation of integrin adhesiveness by application of tensile force by the cytoskeleton, across ligand-integrin-adaptor complexes.

publication date

  • January 2, 2018