|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of the DM domain of human DMRT1 bound to 25mer target DNA== | | ==Crystal structure of the DM domain of human DMRT1 bound to 25mer target DNA== |
| - | <StructureSection load='4yj0' size='340' side='right' caption='[[4yj0]], [[Resolution|resolution]] 3.81Å' scene=''> | + | <StructureSection load='4yj0' size='340' side='right'caption='[[4yj0]], [[Resolution|resolution]] 3.81Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4yj0]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YJ0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YJ0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4yj0]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YJ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YJ0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DMRT1, DMT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DMRT1, DMT1 ([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=4yj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yj0 OCA], [http://pdbe.org/4yj0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yj0 RCSB], [http://www.ebi.ac.uk/pdbsum/4yj0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yj0 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=4yj0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yj0 OCA], [https://pdbe.org/4yj0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yj0 RCSB], [https://www.ebi.ac.uk/pdbsum/4yj0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yj0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/DMRT1_HUMAN DMRT1_HUMAN]] 46,XY complete gonadal dysgenesis. The disease may be caused by mutations affecting the gene represented in this entry. The disease may be caused by mutations affecting the gene represented in this entry. | + | [[https://www.uniprot.org/uniprot/DMRT1_HUMAN DMRT1_HUMAN]] 46,XY complete gonadal dysgenesis. The disease may be caused by mutations affecting the gene represented in this entry. The disease may be caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DMRT1_HUMAN DMRT1_HUMAN]] Transcription factor that plays a key role in male sex determination and differentiation by controlling testis development and male germ cell proliferation. Plays a central role in spermatogonia by inhibiting meiosis in undifferentiated spermatogonia and promoting mitosis, leading to spermatogonial development and allowing abundant and continuous production of sperm. Acts both as a transcription repressor and activator: prevents meiosis by restricting retinoic acid (RA)-dependent transcription and repressing STRA8 expression and promotes spermatogonial development by activating spermatogonial differentiation genes, such as SOHLH1. Also plays a key role in postnatal sex maintenance by maintaining testis determination and preventing feminization: represses transcription of female promoting genes such as FOXL2 and activates male-specific genes. May act as a tumor suppressor. May also play a minor role in oogenesis (By similarity). | + | [[https://www.uniprot.org/uniprot/DMRT1_HUMAN DMRT1_HUMAN]] Transcription factor that plays a key role in male sex determination and differentiation by controlling testis development and male germ cell proliferation. Plays a central role in spermatogonia by inhibiting meiosis in undifferentiated spermatogonia and promoting mitosis, leading to spermatogonial development and allowing abundant and continuous production of sperm. Acts both as a transcription repressor and activator: prevents meiosis by restricting retinoic acid (RA)-dependent transcription and repressing STRA8 expression and promotes spermatogonial development by activating spermatogonial differentiation genes, such as SOHLH1. Also plays a key role in postnatal sex maintenance by maintaining testis determination and preventing feminization: represses transcription of female promoting genes such as FOXL2 and activates male-specific genes. May act as a tumor suppressor. May also play a minor role in oogenesis (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 26: |
Line 26: |
| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Aihara, H]] | | [[Category: Aihara, H]] |
| | [[Category: Banerjee, S]] | | [[Category: Banerjee, S]] |
| Structural highlights
Disease
[DMRT1_HUMAN] 46,XY complete gonadal dysgenesis. The disease may be caused by mutations affecting the gene represented in this entry. The disease may be caused by mutations affecting the gene represented in this entry.
Function
[DMRT1_HUMAN] Transcription factor that plays a key role in male sex determination and differentiation by controlling testis development and male germ cell proliferation. Plays a central role in spermatogonia by inhibiting meiosis in undifferentiated spermatogonia and promoting mitosis, leading to spermatogonial development and allowing abundant and continuous production of sperm. Acts both as a transcription repressor and activator: prevents meiosis by restricting retinoic acid (RA)-dependent transcription and repressing STRA8 expression and promotes spermatogonial development by activating spermatogonial differentiation genes, such as SOHLH1. Also plays a key role in postnatal sex maintenance by maintaining testis determination and preventing feminization: represses transcription of female promoting genes such as FOXL2 and activates male-specific genes. May act as a tumor suppressor. May also play a minor role in oogenesis (By similarity).
Publication Abstract from PubMed
DMRT transcription factors are deeply conserved regulators of metazoan sexual development. They share the DM DNA-binding domain, a unique intertwined double zinc-binding module followed by a C-terminal recognition helix, which binds a pseudopalindromic target DNA. Here we show that DMRT proteins use a unique binding interaction, inserting two adjacent antiparallel recognition helices into a widened DNA major groove to make base-specific contacts. Versatility in how specific base contacts are made allows human DMRT1 to use multiple DNA binding modes (tetramer, trimer and dimer). Chromatin immunoprecipitation with exonuclease treatment (ChIP-exo) indicates that multiple DNA binding modes also are used in vivo. We show that mutations affecting residues crucial for DNA recognition are associated with an intersex phenotype in flies and with male-to-female sex reversal in humans. Our results illuminate an ancient molecular interaction underlying much of metazoan sexual development.
An ancient protein-DNA interaction underlying metazoan sex determination.,Murphy MW, Lee JK, Rojo S, Gearhart MD, Kurahashi K, Banerjee S, Loeuille GA, Bashamboo A, McElreavey K, Zarkower D, Aihara H, Bardwell VJ Nat Struct Mol Biol. 2015 May 25. doi: 10.1038/nsmb.3032. PMID:26005864[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Murphy MW, Lee JK, Rojo S, Gearhart MD, Kurahashi K, Banerjee S, Loeuille GA, Bashamboo A, McElreavey K, Zarkower D, Aihara H, Bardwell VJ. An ancient protein-DNA interaction underlying metazoan sex determination. Nat Struct Mol Biol. 2015 May 25. doi: 10.1038/nsmb.3032. PMID:26005864 doi:http://dx.doi.org/10.1038/nsmb.3032
|
