Decoding WW domain tandem-mediated target recognitions in tissue growth and cell polarity

Abstract
Data availability
Article and author information
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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).

The following data sets were generated

1. Lin Z
2. Yang Z
3. Zhang M
(2019) PDB coordinates KIBRA/LATS1
RCSB Protein Data Bank, 6J68.

http://www.rcsb.org/structure/6J68
1. Lin Z
2. Yang Z
3. Zhang M
(2019) PDB coordinates KIBRA/PTPN14
RCSB Protein Data Bank, 6JJW.

http://www.rcsb.org/structure/6JJW
1. Lin Z
2. Yang Z
3. Zhang M
(2019) PDB coordinates KBIRA/AMOT
RCSB Protein Data Bank, 6JJX.

http://www.rcsb.org/structure/6JJX
1. Lin Z
2. Yang Z
3. Zhang M
(2019) PDB coordinates KIBRA/β-DG
RCSB Protein Data Bank, 6JJY.

http://www.rcsb.org/structure/6JJY
1. Lin Z
2. Yang Z
3. Zhang M
(2019) PDB coordinates MAGI2/Dendrin
RCSB Protein Data Bank, 6JJZ.

http://www.rcsb.org/structure/6JJZ
1. Lin Z
2. Yang Z
3. Zhang M
(2019) PDB coordinates YAP-Linker-Dendrin
RCSB Protein Data Bank, 6JK0.

http://www.rcsb.org/structure/6JK0
1. Lin Z
2. Yang Z
3. Zhang M
(2019) PDB coordinates Dendrin-Linker-YAP
RCSB Protein Data Bank, 6JK1.

http://www.rcsb.org/structure/6JK1

Article and author information

Author details

Zhijie Lin

Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, Hong Kong

Competing interests
No competing interests declared.
Zhou Yang

Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, Hong Kong

Competing interests
No competing interests declared.
Ruiling Xie

Department of Pharmacology, University of California, San Diego, La Jolla, United States

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-6086-8683
Zeyang Ji

Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, Hong Kong

Competing interests
No competing interests declared.
Kunliang Guan

Department of Pharmacology, University of California, San Diego, La Jolla, United States

Competing interests
Kunliang Guan, co-founder and has an equity interest in Vivace Therapeutics, Inc. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies.
Mingjie Zhang

Division of Life Science, State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, Hong Kong

For correspondence
mzhang@ust.hk

Competing interests
Mingjie Zhang, Reviewing editor, eLife.

"This ORCID iD identifies the author of this article:" 0000-0001-9404-0190

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

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.