A redox site involved in integrin activation.
Integrin adhesion receptors contain an on/off switch that regulates ligand binding affinity and cell adhesion. The switch from "off" to "on" is commonly referred to as integrin activation. The objective of this study was to gain insight into the nature of the on/off switch in platelet integrin alpha(IIb)beta(3). Here, we show that a select group of the cysteines, located within the extracellular cysteine-rich domain of the beta subunit, remain unpaired. These unpaired cysteine residues exhibit the properties of a redox site involved in integrin activation. Alterations to the redox site prevent the inter-conversion between resting and active integrin. Altogether, the study establishes integrin as a direct target for redox modulation, revealing an unappreciated link between cell adhesion and redox biology.
Yan
B
B
Program on Cell Adhesion, Cancer Research Center, Burnham Institute, La Jolla, California 92037, USA.
Smith
J W
JW
D000595:Amino Acid Sequence; D003545:Cysteine / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010449:Peptide Mapping; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013438:Sulfhydryl Compounds / Q000378:metabolism
D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013438:Sulfhydryl Compounds; D003545:Cysteine