1xc5
From Proteopedia
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'''Solution Structure of the SMRT Deacetylase Activation Domain''' | '''Solution Structure of the SMRT Deacetylase Activation Domain''' | ||
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[[Category: Neuhaus, D.]] | [[Category: Neuhaus, D.]] | ||
[[Category: Schwabe, J W.R.]] | [[Category: Schwabe, J W.R.]] | ||
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| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 14:50:17 2008'' | |
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Revision as of 11:50, 3 May 2008
Solution Structure of the SMRT Deacetylase Activation Domain
Overview
SMRT (silencing mediator of retinoid acid and thyroid hormone receptor) and NCoR (nuclear receptor corepressor) are transcriptional corepressors that play an essential role in the regulation of development and metabolism. This role is achieved, in part, through the recruitment of a key histone deacetylase (HDAC3), which is itself indispensable for cell viability. The assembly of HDAC3 with the deacetylase activation domain (DAD) of SMRT and NCoR is required for activation of the otherwise inert deacetylase. The DAD comprises an N-terminal DAD-specific motif and a C-terminal SANT (SWI3/ADA2/NCoR/TFIIIB)-like domain. We report here the solution structure of the DAD from SMRT, which reveals a four-helical structure. The DAD differs from the SANT (and MYB) domains in that (i) it has an additional N-terminal helix and (ii) there is a notable hydrophobic groove on the surface of the domain. Structure-guided mutagenesis, combined with interaction assays, showed that residues in the vicinity of the hydrophobic groove are required for interaction with (and hence activation of) HDAC3. Importantly, one surface-exposed lysine is required for activation of HDAC3, but not for interaction. This lysine may play a uniquely important role in the mechanism of activating HDAC3.
About this Structure
1XC5 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural insights into the interaction and activation of histone deacetylase 3 by nuclear receptor corepressors., Codina A, Love JD, Li Y, Lazar MA, Neuhaus D, Schwabe JW, Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):6009-14. Epub 2005 Apr 18. PMID:15837933 Page seeded by OCA on Sat May 3 14:50:17 2008
