Sandbox Reserved 654: Difference between revisions

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The bromodomain is an evolutionary conserved motif found in chromatin remodeling complexes. It has been identified in over 100 proteins from multiple organisms ranging from unicellular microscopic eukaryotes (e.g., yeast) to humans. The motif is best known for the groundbreaking recent discoveries made to identify it as the only acetyl-lysine binding domain<ref> Dhalluin, C. et al (1999) Nature 399, 491 [http://www.nature.com/nature/journal/v399/n6735/abs/399491a0.html]</ref> and to reveal its highly specific ligand selectivity properties<ref> Zeng, L. (2002) FEBS 513:1, 124 [http://www.ncbi.nlm.nih.gov/pubmed/11911891]</ref>. Due to these novel characteristics, bromodomains are typically found in proteins responsible for modifications in chromatin structure and the regulation of gene expression, such as histone acetyltransferases (HATs), and the ATPase subunits of chromatin remodeling complexes. There are several families of proteins with bromodomains. One such family is the human transcriptional coactivator p300/CBP-associated factor (PCAF) bromodomain.

The bromodomain is an evolutionary conserved motif found in chromatin remodeling complexes. It has been identified in over 100 proteins from multiple organisms ranging from unicellular microscopic eukaryotes (e.g., yeast) to humans. The motif is best known for the groundbreaking recent discoveries made to identify it as the only acetyl-lysine binding domain<ref name=a> Dhalluin, C. et al (1999) Nature 399, 491 [http://www.nature.com/nature/journal/v399/n6735/abs/399491a0.html]</ref> and to reveal its highly specific ligand selectivity properties<ref> Zeng, L. (2002) FEBS 513:1, 124 [http://www.ncbi.nlm.nih.gov/pubmed/11911891]</ref>. Due to these novel characteristics, bromodomains are typically found in proteins responsible for modifications in chromatin structure and the regulation of gene expression, such as histone acetyltransferases (HATs), and the ATPase subunits of chromatin remodeling complexes. There are several families of proteins with bromodomains. One such family is the human transcriptional coactivator p300/CBP-associated factor (PCAF) bromodomain.

== '''Structure and Function''' ==

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== Structure ==

The bromodomain was originally identified as a sequence of roughly 60 amino acid residues that forms 2 alpha helices<ref>Haynes, S.R. et al (1992) Nucleic Acids Res. 20, 2603 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC312404/]</ref>. However, it is now known that the bromodomain consist of a highly conserved sequence of approximately 110 amino acids<ref> Owen, D. J. et al. (2000) EMBO J. 19(22), 6141 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC305837/]</ref>. The structure of the PCAF bromodomain consists of a <scene name='Sandbox_Reserved_654/Four-helix/1'>four-helix</scene> bundle (alphaZ, aA,aB, and aC) with a left-handed twist, and a long intervening loop between helices Z and A (ZA loop)~~. Dhalluin~~. The ZA loop of the bromodomain has a defined conformation and is packed against the loop between helices aB and aC (BC loop) to form a hydrophobic pocket. This pocket created by the ZA and BC loops is lined by specific residues (Val 752, Ala 757, Tyr 760, Val 763, Tyr 802 and Tyr 809) that support protein-protein interactions. The ZA loop varies in length between different bromodomains, but almost always contains residues corresponding to Phe 748, Pro 751, Pro 758, Tyr 760 and Pro 767. Dhalluin.

The bromodomain was originally identified as a sequence of roughly 60 amino acid residues that forms 2 alpha helices<ref>Haynes, S.R. et al (1992) Nucleic Acids Res. 20, 2603 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC312404/]</ref>. However, it is now known that the bromodomain consist of a highly conserved sequence of approximately 110 amino acids<ref> Owen, D. J. et al. (2000) EMBO J. 19(22), 6141 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC305837/]</ref>. The structure of the PCAF bromodomain consists of a <scene name='Sandbox_Reserved_654/Four-helix/1'>four-helix</scene> bundle (alphaZ, aA,aB, and aC) with a left-handed twist, and a long intervening loop between helices Z and A (ZA loop)<ref name=a/>. The ZA loop of the bromodomain has a defined conformation and is packed against the loop between helices aB and aC (BC loop) to form a hydrophobic pocket. This pocket created by the ZA and BC loops is lined by specific residues (Val 752, Ala 757, Tyr 760, Val 763, Tyr 802 and Tyr 809) that support protein-protein interactions. The ZA loop varies in length between different bromodomains, but almost always contains residues corresponding to Phe 748, Pro 751, Pro 758, Tyr 760 and Pro 767. Dhalluin.

== Function ==

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 <Structure load='1JM4' size='500' frame='true' align='right' caption='PCAF bromodomain bound to HIV-1 Tat NMR structure' />
-The bromodomain is an evolutionary conserved motif found in chromatin remodeling complexes. It has been identified in over 100 proteins from multiple organisms ranging from unicellular microscopic eukaryotes (e.g., yeast) to humans. The motif is best known for the groundbreaking recent discoveries made to identify it as the only acetyl-lysine binding domain<ref> Dhalluin, C. et al (1999) Nature 399, 491 [http://www.nature.com/nature/journal/v399/n6735/abs/399491a0.html]</ref> and to reveal its highly specific ligand selectivity properties<ref> Zeng, L. (2002) FEBS 513:1, 124 [http://www.ncbi.nlm.nih.gov/pubmed/11911891]</ref>. Due to these novel characteristics, bromodomains are typically found in proteins responsible for modifications in chromatin structure and the regulation of gene expression, such as histone acetyltransferases (HATs), and the ATPase subunits of chromatin remodeling complexes. There are several families of proteins with bromodomains. One such family is the human transcriptional coactivator p300/CBP-associated factor (PCAF) bromodomain.
+The bromodomain is an evolutionary conserved motif found in chromatin remodeling complexes. It has been identified in over 100 proteins from multiple organisms ranging from unicellular microscopic eukaryotes (e.g., yeast) to humans. The motif is best known for the groundbreaking recent discoveries made to identify it as the only acetyl-lysine binding domain<ref name=a> Dhalluin, C. et al (1999) Nature 399, 491 [http://www.nature.com/nature/journal/v399/n6735/abs/399491a0.html]</ref> and to reveal its highly specific ligand selectivity properties<ref> Zeng, L. (2002) FEBS 513:1, 124 [http://www.ncbi.nlm.nih.gov/pubmed/11911891]</ref>. Due to these novel characteristics, bromodomains are typically found in proteins responsible for modifications in chromatin structure and the regulation of gene expression, such as histone acetyltransferases (HATs), and the ATPase subunits of chromatin remodeling complexes. There are several families of proteins with bromodomains. One such family is the human transcriptional coactivator p300/CBP-associated factor (PCAF) bromodomain.
 == '''Structure and Function''' ==
@@ Line 17: / Line 17: @@
 == Structure ==
-The bromodomain was originally identified as a sequence of roughly 60 amino acid residues that forms 2 alpha helices<ref>Haynes, S.R. et al (1992) Nucleic Acids Res. 20, 2603 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC312404/]</ref>. However, it is now known that the bromodomain consist of a highly conserved sequence of approximately 110 amino acids<ref> Owen, D. J. et al. (2000) EMBO J. 19(22), 6141 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC305837/]</ref>. The structure of the PCAF bromodomain consists of a <scene name='Sandbox_Reserved_654/Four-helix/1'>four-helix</scene> bundle (alphaZ, aA,aB, and aC) with a left-handed twist, and a long intervening loop between helices Z and A (ZA loop). Dhalluin. The ZA loop of the bromodomain has a defined conformation and is packed against the loop between helices aB and aC (BC loop) to form a hydrophobic pocket. This pocket created by the ZA and BC loops is lined by specific residues (Val 752, Ala 757, Tyr 760, Val 763, Tyr 802 and Tyr 809) that support protein-protein interactions. The ZA loop varies in length between different bromodomains, but almost always contains residues corresponding to Phe 748, Pro 751, Pro 758, Tyr 760 and Pro 767. Dhalluin.
+The bromodomain was originally identified as a sequence of roughly 60 amino acid residues that forms 2 alpha helices<ref>Haynes, S.R. et al (1992) Nucleic Acids Res. 20, 2603 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC312404/]</ref>. However, it is now known that the bromodomain consist of a highly conserved sequence of approximately 110 amino acids<ref> Owen, D. J. et al. (2000) EMBO J. 19(22), 6141 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC305837/]</ref>. The structure of the PCAF bromodomain consists of a <scene name='Sandbox_Reserved_654/Four-helix/1'>four-helix</scene> bundle (alphaZ, aA,aB, and aC) with a left-handed twist, and a long intervening loop between helices Z and A (ZA loop)<ref name=a/>. The ZA loop of the bromodomain has a defined conformation and is packed against the loop between helices aB and aC (BC loop) to form a hydrophobic pocket. This pocket created by the ZA and BC loops is lined by specific residues (Val 752, Ala 757, Tyr 760, Val 763, Tyr 802 and Tyr 809) that support protein-protein interactions. The ZA loop varies in length between different bromodomains, but almost always contains residues corresponding to Phe 748, Pro 751, Pro 758, Tyr 760 and Pro 767. Dhalluin.
 == Function ==