Decoding WW domain tandem-mediated target recognitions in tissue growth and cell polarity
- Hong Kong University of Science and Technology, Hong Kong
- University of California, San Diego, United States
Abstract
WW domain tandem-containing proteins such as KIBRA, YAP, and MAGI play critical roles in cell growth and polarity via binding to and positioning target proteins in specific subcellular regions. An immense disparity exists between promiscuity of WW domain-mediated target bindings and specific roles of WW domain proteins in cell growth regulation. Here, we discovered that WW domain tandems of KIBRA and MAGI, but not YAP, bind to specific target proteins with extremely high affinity and exquisite sequence specificity. Via systematic structural biology and biochemistry approaches, we decoded the target binding rules of WW domain tandems from cell growth regulatory proteins and uncovered a list of previously unknown WW tandem binding proteins including β-Dystroglycan, JCAD, and PTPN21. The WW tandem-mediated target recognition mechanisms elucidated here can guide functional studies of WW domain proteins in cell growth and polarity as well as in other cellular processes including neuronal synaptic signaling.
Data availability
The atomic coordinates of the WW tandem and target complex structures have been deposited to the Protein Data Bank under the accession codes of: 6J68 (KIBRA/LATS1), 6JJW (KIBRA/PTPN14), 6JJX (KBIRA/AMOT), 6JJY (KIBRA/β-DG), 6JJZ (MAGI2/Dendrin), 6JK0 (YAP-Linker-Dendrin), and 6JK1 (Dendrin-Linker-YAP).
Article and author information
Author details
Funding
Asia Foundation for Cancer Research (AFCR17SC01)
- Mingjie Zhang
National Institutes of Health (CA196878)
- Kunliang Guan
Research Grants Council, University Grants Committee (AOE-M09-12)
- Mingjie Zhang
Research Grants Council, University Grants Committee (C6004-17G)
- Mingjie Zhang
National Institutes of Health (CA217642)
- Kunliang Guan
National Institutes of Health (GM51586)
- Kunliang Guan
National Institutes of Health (DEO15964)
- Kunliang Guan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Lin 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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Decoding WW domain tandem-mediated target recognitions in tissue growth and cell polarity
eLife 8:e49439.
https://doi.org/10.7554/eLife.49439
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