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4h10

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[[Image:4h10.png|left|200px]]
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==Intermolecular recognition revealed by the complex structure of human CLOCK-BMAL1 basic Helix-Loop-Helix domains with E-box DNA==
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<StructureSection load='4h10' size='340' side='right' caption='[[4h10]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4h10]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H10 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4H10 FirstGlance]. <br>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ARNTL, BHLHE5, BMAL1, MOP3, PASD3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), CLOCK, BHLHE8, KIAA0334 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4h10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4h10 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4h10 RCSB], [http://www.ebi.ac.uk/pdbsum/4h10 PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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CLOCK (circadian locomotor output cycles kaput) and BMAL1 (brain and muscle ARNT-like 1) are both transcription factors of the circadian core loop in mammals. Recently published mouse CLOCK-BMAL1 bHLH (basic helix-loop-helix)-PAS (period-ARNT-single-minded) complex structure sheds light on the mechanism for heterodimer formation, but the structural details of the protein-DNA recognition mechanisms remain elusive. Here we have elucidated the crystal structure of human CLOCK-BMAL1 bHLH domains bound to a canonical E-box DNA. We demonstrate that CLOCK and BMAL1 bHLH domains can be mutually selected, and that hydrogen-bonding networks mediate their E-box recognition. We identified a hydrophobic contact between BMAL1 Ile80 and a flanking thymine nucleotide, suggesting that CLOCK-BMAL1 actually reads 7-bp DNA and not the previously believed 6-bp DNA. To find potential non-canonical E-boxes that could be recognized by CLOCK-BMAL1, we constructed systematic single-nucleotide mutations on the E-box and measured their relevant affinities. We defined two non-canonical E-box patterns with high affinities, AACGTGA and CATGTGA, in which the flanking A7-T7' base pair is indispensable for recognition. These results will help us to identify functional CLOCK-BMAL1-binding sites in vivo and to search for clock-controlled genes. Furthermore, we assessed the inhibitory role of potential phosphorylation sites in bHLH regions. We found that the phospho-mimicking mutation on BMAL1 Ser78 could efficiently block DNA binding as well as abolish normal circadian oscillation in cells. We propose that BMAL1 Ser78 should be a key residue mediating input signal-regulated transcriptional inhibition for external cues to entrain the circadian clock by kinase cascade.Cell Research advance online publication 11 December 2012; doi:10.1038/cr.2012.170.
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{{STRUCTURE_4h10| PDB=4h10 | SCENE= }}
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Intermolecular recognition revealed by the complex structure of human CLOCK-BMAL1 basic helix-loop-helix domains with E-box DNA.,Wang Z, Wu Y, Li L, Su XD Cell Res. 2012 Dec 11. doi: 10.1038/cr.2012.170. PMID:23229515<ref>PMID:23229515</ref>
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===Intermolecular recognition revealed by the complex structure of human CLOCK-BMAL1 basic Helix-Loop-Helix domains with E-box DNA===
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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{{ABSTRACT_PUBMED_23229515}}
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== References ==
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<references/>
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==About this Structure==
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__TOC__
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[[4h10]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4H10 OCA].
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</StructureSection>
[[Category: Histone acetyltransferase]]
[[Category: Histone acetyltransferase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Su, X D.]]
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[[Category: Su, X D]]
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[[Category: Wang, Z.]]
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[[Category: Wang, Z]]
[[Category: Bhlh]]
[[Category: Bhlh]]
[[Category: Circadian transcription]]
[[Category: Circadian transcription]]
[[Category: Transcription-dna complex]]
[[Category: Transcription-dna complex]]

Revision as of 13:49, 4 January 2015

Intermolecular recognition revealed by the complex structure of human CLOCK-BMAL1 basic Helix-Loop-Helix domains with E-box DNA

4h10, resolution 2.40Å

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