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  current news   Press   selected story    
     
  22nd February 2010  
 

Structural basis of YAP recognition by TEAD4 in the Hippo pathway

 
 




Authors
Liming Chen#, Siew Wee Chan#, XiaoQian Zhang, Martin Walsh, Chun Jye Lim, Wanjin Hong* and Haiwei Song*.

# These authors contributed equally to this work
*Corresponding authors

Abstract
The Hippo signaling pathway controls cell growth, proliferation, and apoptosis by regulating the expression of target genes that execute these processes. Acting downstream of this pathway is the YAP transcriptional co-activator, whose biological function is mediated by the conserved TEAD family transcription factors. The interaction of YAP with TEADs is critical to regulate Hippo pathway-responsive genes. Here, we describe the crystal structure of YAP-interacting C-terminal domain of TEAD4 in complex with TEAD-interacting N-terminal domain of YAP. The structure reveals that the N-terminal region of YAP is folded into two short helices with an extended loop containing the PXXΦP motif in between, while the C-terminal domain of TEAD4 has an immunoglobulin-like fold. YAP interacts with TEAD4 mainly through the two short helices. Point mutations of TEAD4 indicate that the residues important for YAP interaction are required for its transforming activity. Mutagenesis reveals that the PXXΦP motif of YAP, although making few contacts with TEAD4, is important for TEAD4 interaction as well as for the transforming activity.


 
 

 
 


Figure Legend:
(A) A ribbon diagram of the TEAD4-YAP complex. TEAD4 and YAP are shown in green and pink, respectively, and the PXXΦP motif in YAP is colored in cyan. Secondary structure for both TEAD4 and YAP are marked. (B) Surface view of TEAD4 (green) with bound YAP in ribbon diagram (pink with the PXXΦP motif in cyan). The view is as in (A). (C) Residues in TEAD4 involved in interactions with YAP are important for anchorage-independent cell growth. (D) The PXXΦP containing loop of YAP is essential for TEAD4 interaction as well as for the transforming activity of YAP.

Published in Genes and Development, 2010 Feb 1;24(3):290-300

For more information on Prof. Wanjin Hong's Laboratory, please click here.

For more information on Prof. Haiwei Song's Laboratory, please click here.