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| | ==NMR Structure of A13 homedomain== | | ==NMR Structure of A13 homedomain== |
| - | <StructureSection load='2l7z' size='340' side='right' caption='[[2l7z]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> | + | <StructureSection load='2l7z' size='340' side='right'caption='[[2l7z]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2l7z]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L7Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2L7Z FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2l7z]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L7Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L7Z FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HOXA13, HOX1J ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HOXA13, HOX1J ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2l7z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l7z OCA], [http://pdbe.org/2l7z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2l7z RCSB], [http://www.ebi.ac.uk/pdbsum/2l7z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2l7z ProSAT]</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=2l7z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l7z OCA], [https://pdbe.org/2l7z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l7z RCSB], [https://www.ebi.ac.uk/pdbsum/2l7z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l7z ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/HXA13_HUMAN HXA13_HUMAN]] Hand-foot-genital syndrome;Guttmacher syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | + | [[https://www.uniprot.org/uniprot/HXA13_HUMAN HXA13_HUMAN]] Hand-foot-genital syndrome;Guttmacher syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HXA13_HUMAN HXA13_HUMAN]] Sequence-specific, AT-rich binding transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. | + | [[https://www.uniprot.org/uniprot/HXA13_HUMAN HXA13_HUMAN]] Sequence-specific, AT-rich binding transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Ames, J]] | | [[Category: Ames, J]] |
| | [[Category: Gene regulation]] | | [[Category: Gene regulation]] |
| | [[Category: Hoxa13]] | | [[Category: Hoxa13]] |
| Structural highlights
Disease
[HXA13_HUMAN] Hand-foot-genital syndrome;Guttmacher syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
[HXA13_HUMAN] Sequence-specific, AT-rich binding transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.
Publication Abstract from PubMed
The homeobox gene (HOXA13) codes for a transcription factor protein that binds to AT-rich DNA sequences and controls expression of genes during embryonic morphogenesis. Here we present the NMR structure of HOXA13 homeodomain (A13DBD) bound to an 11-mer DNA duplex. A13DBD forms a dimer that binds to DNA with a dissociation constant of 7.5 nM. The A13DBD/DNA complex has a molar mass of 35 kDa consistent with two molecules of DNA bound at both ends of the A13DBD dimer. A13DBD contains an N-terminal arm (residues 324 - 329) that binds in the DNA minor groove, and a C-terminal helix (residues 362 - 382) that contacts the ATAA nucleotide sequence in the major groove. The N370 side-chain forms hydrogen bonds with the purine base of A5* (base paired with T5). Side-chain methyl groups of V373 form hydrophobic contacts with the pyrimidine methyl groups of T5, T6* and T7*, responsible for recognition of TAA in the DNA core. I366 makes similar methyl contacts with T3* and T4*. Mutants (I366A, N370A and V373G) all have decreased DNA binding and transcriptional activity. Exposed protein residues (R337, K343, and F344) make intermolecular contacts at the protein dimer interface. The mutation F344A weakens protein dimerization and lowers transcriptional activity by 76%. We conclude that the non-conserved residue, V373 is critical for structurally recognizing TAA in the major groove, and that HOXA13 dimerization is required to activate transcription of target genes.
Structural basis for sequence specific DNA binding and protein dimerization of HOXA13.,Zhang Y, Larsen CA, Stadler HS, Ames JB PLoS One. 2011;6(8):e23069. Epub 2011 Aug 1. PMID:21829694[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhang Y, Larsen CA, Stadler HS, Ames JB. Structural basis for sequence specific DNA binding and protein dimerization of HOXA13. PLoS One. 2011;6(8):e23069. Epub 2011 Aug 1. PMID:21829694 doi:10.1371/journal.pone.0023069
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