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| | ==Solution NMR-derived complex structure of Hoxa13 DNA binding domain bound to DNA== | | ==Solution NMR-derived complex structure of Hoxa13 DNA binding domain bound to DNA== |
| - | <StructureSection load='2ld5' size='340' side='right'caption='[[2ld5]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2ld5' size='340' side='right'caption='[[2ld5]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ld5]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LD5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LD5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ld5]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LD5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LD5 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Hox-1.10, Hoxa13 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | </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=2ld5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ld5 OCA], [https://pdbe.org/2ld5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ld5 RCSB], [https://www.ebi.ac.uk/pdbsum/2ld5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ld5 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=2ld5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ld5 OCA], [https://pdbe.org/2ld5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ld5 RCSB], [https://www.ebi.ac.uk/pdbsum/2ld5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ld5 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[https://www.uniprot.org/uniprot/HXA13_MOUSE HXA13_MOUSE]] Defects in Hoxa13 are the cause of hypodactyly (Hd), a condition characterized by profound deficiency of digital arch structures.
| + | [https://www.uniprot.org/uniprot/HXA13_MOUSE HXA13_MOUSE] Defects in Hoxa13 are the cause of hypodactyly (Hd), a condition characterized by profound deficiency of digital arch structures. |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/HXA13_MOUSE HXA13_MOUSE]] 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 (By similarity).
| + | [https://www.uniprot.org/uniprot/HXA13_MOUSE HXA13_MOUSE] 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 (By similarity). |
| | <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: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Zhang, Y]] | + | [[Category: Zhang Y]] |
| - | [[Category: Transcription-dna complex]]
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| Structural highlights
Disease
HXA13_MOUSE Defects in Hoxa13 are the cause of hypodactyly (Hd), a condition characterized by profound deficiency of digital arch structures.
Function
HXA13_MOUSE 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 (By similarity).
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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