1n72: Difference between revisions

Revision as of 15:02, 21 February 2008

Structure and Ligand of a Histone Acetyltransferase Bromodomain

OverviewOverview

Histone acetylation is important in chromatin remodelling and gene activation. Nearly all known histone-acetyltransferase (HAT)-associated transcriptional co-activators contain bromodomains, which are approximately 110-amino-acid modules found in many chromatin-associated proteins. Despite the wide occurrence of these bromodomains, their three-dimensional structure and binding partners remain unknown. Here we report the solution structure of the bromodomain of the HAT co-activator P/CAF (p300/CBP-associated factor). The structure reveals an unusual left-handed up-and-down four-helix bundle. In addition, we show by a combination of structural and site-directed mutagenesis studies that bromodomains can interact specifically with acetylated lysine, making them the first known protein modules to do so. The nature of the recognition of acetyl-lysine by the P/CAF bromodomain is similar to that of acetyl-CoA by histone acetyltransferase. Thus, the bromodomain is functionally linked to the HAT activity of co-activators in the regulation of gene transcription.

About this StructureAbout this Structure

1N72 is a Single protein structure of sequence from Homo sapiens. This structure supersedes the now removed PDB entry 1B91. Active as Histone acetyltransferase, with EC number 2.3.1.48 Full crystallographic information is available from OCA.

ReferenceReference

Structure and ligand of a histone acetyltransferase bromodomain., Dhalluin C, Carlson JE, Zeng L, He C, Aggarwal AK, Zhou MM, Nature. 1999 Jun 3;399(6735):491-6. PMID:10365964

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OCA

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-[[Image:1n72.gif|left|200px]]<br />
+[[Image:1n72.gif|left|200px]]<br /><applet load="1n72" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1n72" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1n72" />
 '''Structure and Ligand of a Histone Acetyltransferase Bromodomain'''<br />
 ==Overview==
-Histone acetylation is important in chromatin remodelling and gene, activation. Nearly all known histone-acetyltransferase (HAT)-associated, transcriptional co-activators contain bromodomains, which are, approximately 110-amino-acid modules found in many chromatin-associated, proteins. Despite the wide occurrence of these bromodomains, their, three-dimensional structure and binding partners remain unknown. Here we, report the solution structure of the bromodomain of the HAT co-activator, P/CAF (p300/CBP-associated factor). The structure reveals an unusual, left-handed up-and-down four-helix bundle. In addition, we show by a, combination of structural and site-directed mutagenesis studies that, bromodomains can interact specifically with acetylated lysine, making them, the first known protein modules to do so. The nature of the recognition of, acetyl-lysine by the P/CAF bromodomain is similar to that of acetyl-CoA by, histone acetyltransferase. Thus, the bromodomain is functionally linked to, the HAT activity of co-activators in the regulation of gene transcription.
+Histone acetylation is important in chromatin remodelling and gene activation. Nearly all known histone-acetyltransferase (HAT)-associated transcriptional co-activators contain bromodomains, which are approximately 110-amino-acid modules found in many chromatin-associated proteins. Despite the wide occurrence of these bromodomains, their three-dimensional structure and binding partners remain unknown. Here we report the solution structure of the bromodomain of the HAT co-activator P/CAF (p300/CBP-associated factor). The structure reveals an unusual left-handed up-and-down four-helix bundle. In addition, we show by a combination of structural and site-directed mutagenesis studies that bromodomains can interact specifically with acetylated lysine, making them the first known protein modules to do so. The nature of the recognition of acetyl-lysine by the P/CAF bromodomain is similar to that of acetyl-CoA by histone acetyltransferase. Thus, the bromodomain is functionally linked to the HAT activity of co-activators in the regulation of gene transcription.
 ==About this Structure==
-N72 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure superseeds the now removed PDB entry 1B91. Active as [http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1N72 OCA].
+N72 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry 1B91. Active as [http://en.wikipedia.org/wiki/Histone_acetyltransferase Histone acetyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.48 2.3.1.48] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N72 OCA].
 ==Reference==
@@ Line 15: / Line 14: @@
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
-[[Category: Aggarwal, A.K.]]
+[[Category: Aggarwal, A K.]]
-[[Category: Carlson, J.E.]]
+[[Category: Carlson, J E.]]
 [[Category: Dhalluin, C.]]
 [[Category: He, C.]]
 [[Category: Zeng, L.]]
-[[Category: Zhou, M.M.]]
+[[Category: Zhou, M M.]]
 [[Category: 4-helical bundle]]
 [[Category: histone acetyltransferase bromodomain]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 18:18:35 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:02:59 2008''