PT  - JOURNAL ARTICLE
AU  - Zhijie Lin
AU  - Zhou Yang
AU  - Ruiling Xie
AU  - Zeyang Ji
AU  - Kunliang Guan
AU  - Mingjie Zhang
TI  - Decoding WW Domain Tandem-mediated Target Recognitions in Tissue Growth and Cell Polarity
AID  - 10.1101/694976
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 694976
4099  - http://biorxiv.org/content/early/2019/07/07/694976.short
4100  - http://biorxiv.org/content/early/2019/07/07/694976.full
AB  - 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 scaffold 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 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 such as 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.