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| | ==Crystal structure of HHM (human homologue of murine maternal Id-like molecule)== | | ==Crystal structure of HHM (human homologue of murine maternal Id-like molecule)== |
| - | <StructureSection load='3ay5' size='340' side='right' caption='[[3ay5]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='3ay5' size='340' side='right'caption='[[3ay5]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ay5]] is a 1 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=3AY5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3AY5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ay5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3AY5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3AY5 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CCNDBP1, DIP1, GCIP, HHM ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5Å</td></tr> |
| - | <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=3ay5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ay5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ay5 RCSB], [http://www.ebi.ac.uk/pdbsum/3ay5 PDBsum]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3ay5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ay5 OCA], [https://pdbe.org/3ay5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ay5 RCSB], [https://www.ebi.ac.uk/pdbsum/3ay5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ay5 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CCDB1_HUMAN CCDB1_HUMAN]] May negatively regulate cell cycle progression. May act at least in part via inhibition of the cyclin-D1/CDK4 complex, thereby preventing phosphorylation of RB1 and blocking E2F-dependent transcription.<ref>PMID:10801854</ref> | + | [https://www.uniprot.org/uniprot/CCDB1_HUMAN CCDB1_HUMAN] May negatively regulate cell cycle progression. May act at least in part via inhibition of the cyclin-D1/CDK4 complex, thereby preventing phosphorylation of RB1 and blocking E2F-dependent transcription.<ref>PMID:10801854</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Helix-loop-helix (HLH) family transcription factors regulate numerous developmental and homeostatic processes. Dominant-negative HLH (dnHLH) proteins lack DNA-binding ability and capture basic HLH (bHLH) transcription factors to inhibit cellular differentiation and enhance cell proliferation and motility, thus participating in patho-physiological processes. We report the first structure of a free-standing human dnHLH protein, HHM (Human homologue of murine maternal Id-like molecule). HHM adopts a V-shaped conformation, with N-terminal and C-terminal five-helix bundles connected by the HLH region. In striking contrast to the common HLH, the HLH region in HHM is extended, with its hydrophobic dimerization interfaces embedded in the N- and C-terminal helix bundles. Biochemical and physicochemical analyses revealed that HHM exists in slow equilibrium between this V-shaped form and the partially unfolded, relaxed form. The latter form is readily available for interactions with its target bHLH transcription factors. Mutations disrupting the interactions in the V-shaped form compromised the target transcription factor specificity and accelerated myogenic cell differentiation. Therefore, the V-shaped form of HHM may represent an autoinhibited state, and the dynamic conformational equilibrium may control the target specificity.
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| - | Structure of a dominant-negative helix-loop-helix transcriptional regulator suggests mechanisms of autoinhibition.,Ishii R, Isogaya K, Seto A, Koinuma D, Watanabe Y, Arisaka F, Yaguchi S, Ikushima H, Dohmae N, Miyazono K, Miyazawa K, Ishitani R, Nureki O EMBO J. 2012 Mar 27;31(11):2541-52. doi: 10.1038/emboj.2012.77. PMID:22453338<ref>PMID:22453338</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: Ishitani, R]] | + | [[Category: Large Structures]] |
| - | [[Category: Nureki, O]] | + | [[Category: Ishitani R]] |
| - | [[Category: Seto, A]] | + | [[Category: Nureki O]] |
| - | [[Category: Cell cycle]] | + | [[Category: Seto A]] |
| - | [[Category: Dominant-negative helix-loop-helix transcriptional regulator]]
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