The Platelet Integrin αIIbβ3 Has an Endogenous Thiol Isomerase Activity*
By S. O’neill, A. Robinson, A. Deering, M. Ryan, D. Fitzgerald, N. Moran. Journal of Biological Chemistry, 2000
88 citations recorded by the source corpus.
Integrins are cysteine-rich heterodimeric cell-surface adhesion molecules that alter their affinity for ligands in response to cellular activation. The molecular mechanisms involved in this activation of integrins are not understood. Treatment with the thiol-reducing agent, dithiothreitol, can induce an activation-like state in many integrins suggesting that cysteine-cysteine dithiol bonds are important for the receptor's tertiary structure and may be involved in activation-induced conformational changes. Here we demonstrate that the platelet-specific integrin, αIIbβ3, contains an endogenous thiol isomerase activity, predicted from the presence of the tetrapeptide motif, CXXC, in each of the cysteine-rich repeats of the β3 polypeptide. This motif comprises the active site in enzymes involved in disulfide exchange reactions, including protein-disulfide isomerase (EC 5.3.4.1) and thioredoxin. Intrinsic thiol isomerase activity is also observed in the related integrin, αvβ3, which shares a common β-subunit. Thiol isomerase activity within αIIbβ3 is time-dependent and saturable, and is inhibited by the protein-disulfide isomerase inhibitor, bacitracin. Furthermore, this activity is calcium-sensitive and is regulated in the EDTA-stabilized conformation of the integrin. This novel demonstration of an enzymatic activity associated with an integrin subunit suggests that altered thiol bonding within the integrin or its substrates may be locally modified during αIIbβ3 activation.
Subfields: Hematology, Immunology and Allergy, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/980010f89fee423bee453696e7383f16000a7c73
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Citations in the corpus
- Enzymatically catalyzed disulfide exchange is required for platelet adhesion to collagen via integrin α2β1 (2003, background): “This disulfide exchange appears to be controlled by protein-disulfide isomerase activity (11,12), provided either by activity intrinsic to the integrin (16), or by protein disulfide isomerase (PDI) present on the platelet surface (17-20).”