On the nature of low- and high-affinity EGF receptors on living cells

摘要: The small subpopulation of high-affinity EGF receptors (EGFRs) on living cells revealed by Scatchard analysis 125I-EGF binding results was discovered nearly three decades ago, yet not much is known about the underlying mechanism. After determination structure different forms EGFR extracellular domain it proposed that monomeric tethered configuration corresponds to majority low-affinity receptors, whereas extended dimeric minority class EGFRs. Mathematical modeling EGF-binding experiments conformational mutants has shown does correspond and can only be accounted for including in mathematical model an additional event attributed dynamic nature cells. To circumvent this problem we have performed similar background mutant form sites. Quantitative these data show release intramolecular tether causes a 2-fold increase affinity, elimination dimerization arm reduces affinity ≈6-fold. These confirm salient features structural regulation argue further provides limited autoinhibitory control activity sites reflects interconverting, tethered, receptor configurations.