Ligand binding to WW tandem domains of YAP2 transcriptional regulator is under negative cooperativity.
Ligand binding to WW tandem domains of YAP2 transcriptional regulator is under negative cooperativity.
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配体与YAP2转录调节剂的WW串联结构域的结合在负合作下。
DOI：
10.1111/febs.13095
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发表时间：
2014-12
期刊：
影响因子：
--
通讯作者：
Farooq A
中科院分区：
文献类型：
--
作者：
Schuchardt BJ;Mikles DC;Hoang LM;Bhat V;McDonald CB;Sudol M;Farooq A
YAP2 transcriptional regulator drives a multitude of cellular processes, including the newly discovered Hippo tumor suppressor pathway, by virtue of the ability of its WW domains to bind and recruit PPXY-containing ligands to specific subcellular compartments. Herein, we employ an array of biophysical tools to investigate allosteric communication between the WW tandem domains of YAP2. Our data show that the WW tandem domains of YAP2 negatively cooperate when binding to their cognate ligands. Moreover, the molecular origin of such negative cooperativity lies in an unfavorable entropic contribution to the overall free energy relative to ligand binding to isolated WW domains. Consistent with this notion, the WW tandem domains adopt a fixed spatial orientation such that the WW1 domain curves outwards and stacks onto the binding groove of WW2 domain, thereby sterically hindering ligand binding to both itself and its tandem partner. Although ligand binding to both WW domains disrupts such interdomain stacking interaction, they reorient themselves and adopt an alternative fixed spatial orientation in the liganded state by virtue of their ability to engage laterally so as to allow their binding grooves to point outwards and away from each other. In short, while the ability of WW tandem domains to aid ligand binding is well-documented, our demonstration that they may also be subject to negative binding cooperativity represents a paradigm shift in our understanding of the molecular action of this ubiquitous family of protein modules.
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影响因子：
3.5
作者：
Gaffney CJ;Oka T;Mazack V;Hilman D;Gat U;Muramatsu T;Inazawa J;Golden A;Carey DJ;Farooq A;Tromp G;Sudol M
通讯作者：
Sudol M
影响因子：
4.8
作者：
Huang, Xiaojuan;Beullens, Monique;Shi, Yunyu
通讯作者：
Shi, Yunyu
影响因子：
4.8
作者：
Chen, HI;Einbond, A;Sudol, M
通讯作者：
Sudol, M
DOI：
10.1038/77923
发表时间：
2000-08-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Huang, X;Poy, F;Eck, MJ
通讯作者：
Eck, MJ
影响因子：
10.5
作者：
Aragon, Eric;Goerner, Nina;Macias, Maria J.
通讯作者：
Macias, Maria J.