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Autopalmitoylation of TEAD proteins regulates transcriptional output of the Hippo pathway

Autopalmitoylation of TEAD proteins regulates transcriptional output of the Hippo pathwayTEA domain (TEAD) transcription factors bind to the coactivators YAP and TAZ and regulate the transcriptional output of the Hippo pathway, playing critical roles in organ size control and tumorigenesis. Protein S-palmitoylation attaches a fatty acid, palmitate, to cysteine residues and regulates protein trafficking, membrane localization and signaling activities. Using activity- based chemical probes, we discovered that human TEADs possess intrinsic palmitoylating enzyme–like activities and undergo autopalmitoylation at evolutionarily conserved cysteine residues under physiological conditions. We determined the crystal structures of lipid-bound TEADs and found that the lipid chain of palmitate inserts into a conserved deep hydrophobic pocket. Strikingly, palmitoylation did not alter TEAD’s localization, but it was required for TEAD’s binding to YAP and TAZ and was dispensable for its binding to the Vgll4 tumor suppressor. Moreover, palmitoylation-deficient TEAD mutants impaired TAZ- mediated muscle differentiation in vitro and tissue overgrowth mediated by the Drosophila YAP homolog Yorkie in vivo. Our study directly links autopalmitoylation to the transcriptional regulation of the Hippo pathway.

Nat Chem Biol. 2016 Apr;12(4):282-9.
doi: 10.1038/nchembio.2036. Epub 2016 Feb 22.

 

Nature Publishing Group

© 2016 Macmillan Publishers Limited.

  Chan P, Han X, Zheng B, DeRan M, Yu J, Jarugumilli GK, Deng H, Pan D, Luo X, Wu X.Yu H.

Another SBC Highlight:

Structural basis of cohesin cleavage by separase
Molecular mechanism of respiratory syncytial virus fusion inhibitors

Accurate chromosome segregation requires timely dissolution of chromosome cohesion after chromosomes are properly attached to the mitotic spindle. Separase is absolutely essential for cohesion dissolution in organisms from yeast to man.

 

Nature. 2016 Apr 7;532(7597):131-4.
doi: 10.1038/nature17402. Epub 2016 Mar 30.

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SBC Announcements:

 

19-ID Pilatus Detector

SBC is pleased to announce the introduction of a Pilatus 3 X 6M detector into the User Program at beamline 19-ID.
Data collected by our users has been of outstanding quality.

 

 

 

19-BM Rebotic sample mounter available

A robot is now available for use at beamline 19-BM. The sample dewar accommodates ten Unipuck magazines; pins must be 18mm in length and use either SSRL or ALS bases. Experienced users may now request remote access to 19-BM when applying for beamtime.

 

 

 

ALSO: Please Be Aware...!

 

APS requests the Experimental Safety Approval Form (ESAF) be submitted at least seven days prior to your scheduled beamtime.

 

Failure to submit your ESAF in advance may result in delaying the beginning of your experiment.

 

Rapid Access Beamtime Available:

SBC Beamtime Request System

The on-line SBC Beamtime Request System allows users to view available beamtime on 19-ID and 19-BM, and to submit a request for rapid beamtime allocation.

Beamtime is available to the research community via a peer reviewed proposal system; it is supported by the U.S. Department of Energy, Office of Biological and Environmental Research.

Current Beamline Statistics:

APS PDB Depositions from BioSync
SBC Sector 19 2014 2015 2016 TOTAL
ID BM ID BM ID BM
PDB Depositions 263 36 218 24 39 10 4729

APS Publications Database:

Publications Total
SBC-CAT Publication List: 19-ID 1400
SBC-CAT Publication List: 19-BM 519
SBC-CAT Publication List: ALL
APS Publications Database

MCSG / APCF Announcements:

 

Beginning August 01, 2015 the Midwest Center for Structural Genomics (MCSG) will start accepting applications for access to the MCSG User Resource.

 

MCSG's structure determination platform is well established, and combines technologies, robotics and expertise for gene cloning, protein production, and crystallization, as well as biochemical and biophysical characterization.

 

For further information, please contact Andrzej Joachimiak.

 

Future Meetings:

 

Protein Society: 30th Anniversary Symposium

July 16-19, 2016

Hyatt Regency Baltimore; Baltimore MD

 

American Crystallographic Association, 2016

July 22-26, 2016

Downtown Sheraton Hotel; Denver CO

 

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