Autoinhibition of ankyrin-B/G membrane target bindings by intrinsically disordered segments from the tail regions
- The Hong Kong University of Science and Technology, Hong Kong
- Hong Kong University of Science and Technology, China
- University of Science and Technology of China, China
- South University of Science and Technology of China, China
Abstract
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.
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Funding
Research Grants Council, University Grants Committee (663812)
- Mingjie Zhang
Ministry of Science and Technology of the People's Republic of China (2014CB910204)
- Mingjie Zhang
Research Grants Council, University Grants Committee (664113)
- Mingjie Zhang
Research Grants Council, University Grants Committee (16103614)
- Mingjie Zhang
Research Grants Council, University Grants Committee (AoE-M09-12)
- Mingjie Zhang
Ministry of Science and Technology of the People's Republic of China (2016YFA0501900)
- Mingjie Zhang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Chen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Autoinhibition of ankyrin-B/G membrane target bindings by intrinsically disordered segments from the tail regions
eLife 6:e29150.
https://doi.org/10.7554/eLife.29150
