The affinity of integrins for matrix components can be modulated by changes to their cytoplasmic domains: a process known as inside-out signaling. You have identified a key region in the cytoplasmic domains of α_IIbβ₃ integrin that seems to be required for inside-out signaling (Figure Q19–3). Substitution of alanine for either D723 in the β chain or R995 in the α chain leads to a high level of spontaneous activation, under conditions where the wild-type chains are inactive. Your advisor suggests that you convert the aspartate in the β chain to an arginine (D723R) and the arginine in the α chain to an aspartate (R995D). You compare all three α chains (R995, R995A, and R995D) against all three β chains (D723, D723A, and D723R). You find that all pairs have a high level of spontaneous activation, except D723 vs R995 (the wild type) and D723R vs R995D, which have low levels. Based on these results, how do you think the α_IIbβ₃ integrin is held in its inactive state?

Figure Q19-3

Transcribed Image Text:

extracellular plasma membrane cytoplasm space 723 B3 -WKLLITIHDRKEF COOH WKVGFFKRNRP- COOH 995