4atk: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[ | ==MITF:E-box complex== | ||
<StructureSection load='4atk' size='340' side='right' caption='[[4atk]], [[Resolution|resolution]] 2.95Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4atk]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ATK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ATK FirstGlance]. <br> | |||
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ath|4ath]], [[4ati|4ati]]</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=4atk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4atk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4atk RCSB], [http://www.ebi.ac.uk/pdbsum/4atk PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Microphthalmia-associated transcription factor (MITF) is a master regulator of melanocyte development and an important oncogene in melanoma. MITF heterodimeric assembly with related basic helix-loop-helix leucine zipper transcription factors is highly restricted, and its binding profile to cognate DNA sequences is distinct. Here, we determined the crystal structure of MITF in its apo conformation and in the presence of two related DNA response elements, the E-box and M-box. In addition, we investigated mouse and human Mitf mutations to dissect the functional significance of structural features. Owing to an unusual three-residue shift in the leucine zipper register, the MITF homodimer shows a marked kink in one of the two zipper helices to allow an out-of-register assembly. Removal of this insertion relieves restricted heterodimerization by MITF and permits assembly with the transcription factor MAX. Binding of MITF to the M-box motif is mediated by an unusual nonpolar interaction by Ile212, a residue that is mutated in mice and humans with Waardenburg syndrome. As several related transcription factors have low affinity for the M-box sequence, our analysis unravels how these proteins discriminate between similar target sequences. Our data provide a rational basis for targeting MITF in the treatment of important hereditary diseases and cancer. | |||
Restricted leucine zipper dimerization and specificity of DNA recognition of the melanocyte master regulator MITF.,Pogenberg V, Ogmundsdottir MH, Bergsteinsdottir K, Schepsky A, Phung B, Deineko V, Milewski M, Steingrimsson E, Wilmanns M Genes Dev. 2012 Dec 1;26(23):2647-58. doi: 10.1101/gad.198192.112. PMID:23207919<ref>PMID:23207919</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
== | __TOC__ | ||
</StructureSection> | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Deineko, V | [[Category: Deineko, V]] | ||
[[Category: Pogenberg, V | [[Category: Pogenberg, V]] | ||
[[Category: Wilmanns, M | [[Category: Wilmanns, M]] | ||
[[Category: Dna binding protein-dna complex]] | [[Category: Dna binding protein-dna complex]] | ||
[[Category: Dna-binding protein-dna complex]] | [[Category: Dna-binding protein-dna complex]] | ||
[[Category: Melanoma]] | [[Category: Melanoma]] | ||
[[Category: Transcription factor]] | [[Category: Transcription factor]] | ||