TY - JOUR TI - Autoinhibition of ankyrin-B/G membrane target bindings by intrinsically disordered segments from the tail regions AU - Chen, Keyu AU - Li, Jianchao AU - Wang, Chao AU - Wei, Zhiyi AU - Zhang, Mingjie A2 - Brunger, Axel T VL - 6 PY - 2017 DA - 2017/08/25 SP - e29150 C1 - eLife 2017;6:e29150 DO - 10.7554/eLife.29150 UR - https://doi.org/10.7554/eLife.29150 AB - Ankyrins together with their spectrin partners are the master organizers of micron-scale membrane domains in diverse tissues. The 24 ankyrin (ANK) repeats of ankyrins bind to numerous membrane proteins, linking them to spectrin-based cytoskeletons at specific membrane microdomains. The accessibility of the target binding groove of ANK repeats must be regulated to achieve spatially defined functions of ankyrins/target complexes in different tissues, though little is known in this regard. Here we systemically investigated the autoinhibition mechanism of ankyrin-B/G by combined biochemical, biophysical and structural biology approaches. We discovered that the entire ANK repeats are inhibited by combinatorial and quasi-independent bindings of multiple disordered segments located in the ankyrin-B/G linkers and tails, suggesting a mechanistic basis for differential regulations of membrane target bindings by ankyrins. In addition to elucidating the autoinhibition mechanisms of ankyrins, our study may also shed light on regulations on target bindings by other long repeat-containing proteins. KW - Ankyrin-R/B/G KW - ankyrin repeats KW - autoinhibition KW - axon initial segment JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -