Mechanisms by which I kappa B proteins control NF-kappa B activity

The biological activity of the transcription factor NF-kappa B is different ially controlled by three I kappa B proteins, I kappa B alpha, I kappa B be ta, and I kappa B epsilon. We have examined the molecular basis for the dif ferential inhibitory strengths of I kappa B proteins by constructing hybrid I kappa Bs and found that the first ankyrin repeat of I kappa Ba is respon sible for its strong inhibitory effect. Swapping a putative beta-turn withi n the first ankyrin repeat between the strong I kappa B alpha and the weak I kappa B beta inhibitors switches their in vivo inhibitory activity on NF- kappa B. The qualitatively distinct contacts made by this p-turn in I kappa B alpha and I kappa B beta with NF-kappa B determine the efficiency by whi ch I kappa Bs sequester NF-kappa B to the cytoplasm, thus explaining their distinct effects on gene activity.