View source for 1hrz


==THE 3D STRUCTURE OF THE HUMAN SRY-DNA COMPLEX SOLVED BY MULTI-DIMENSIONAL HETERONUCLEAR-EDITED AND-FILTERED NMR==
<StructureSection load='1hrz' size='340' side='right'caption='[[1hrz]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1hrz]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HRZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HRZ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1hrz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hrz OCA], [https://pdbe.org/1hrz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hrz RCSB], [https://www.ebi.ac.uk/pdbsum/1hrz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hrz ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SRY_HUMAN SRY_HUMAN] Defects in SRY are the cause of 46,XY sex reversal type 1 (SRXY1) [MIM:[https://omim.org/entry/400044 400044]. A condition characterized by male-to-female sex reversal in the presence of a normal 46,XY karyotype. Patients manifest rapid and early degeneration of their gonads, which are present in the adult as 'streak gonads', consisting mainly of fibrous tissue and variable amounts of ovarian stroma. As a result these patients do not develop secondary sexual characteristics at puberty. The external genitalia in these subjects are completely female, and Muellerian structures are normal.<ref>PMID:11563911</ref> <ref>PMID:2247149</ref> <ref>PMID:8353496</ref> <ref>PMID:1570829</ref> <ref>PMID:1415266</ref> <ref>PMID:1339396</ref> <ref>PMID:8447323</ref> <ref>PMID:1483689</ref> <ref>PMID:8105086</ref> <ref>PMID:8019555</ref> <ref>PMID:7985018</ref> <ref>PMID:7717397</ref> <ref>PMID:7776083</ref> [:]<ref>PMID:9678356</ref> <ref>PMID:9521592</ref> <ref>PMID:9450909</ref> <ref>PMID:10670762</ref> [:]<ref>PMID:10852465</ref> <ref>PMID:10843173</ref> <ref>PMID:10721678</ref> <ref>PMID:12107262</ref> <ref>PMID:12793612</ref> <ref>PMID:17063144</ref>   Note=A 45,X chromosomal aberration involving SRY is found in Turner syndrome, a disease characterized by gonadal dysgenesis with short stature, "streak gonads", variable abnormalities such as webbing of the neck, cubitus valgus, cardiac defects, low posterior hair line. The phenotype is female.  Defects in SRY are the cause of 46,XX sex reversal type 1 (SRXX1) [MIM:[https://omim.org/entry/400045 400045]. A condition in which male gonads develop in a genetic female (female to male sex reversal).<ref>PMID:9652903</ref> <ref>PMID:10602113</ref> 
== Function ==
[https://www.uniprot.org/uniprot/SRY_HUMAN SRY_HUMAN] Transcriptional regulator that controls a genetic switch in male development. It is necessary and sufficient for initiating male sex determination by directing the development of supporting cell precursors (pre-Sertoli cells) as Sertoli rather than granulosa cells (By similarity). In male adult brain involved in the maintenance of motor functions of dopaminergic neurons (By similarity). Involved in different aspects of gene regulation including promoter activation or repression (By similarity). Promotes DNA bending. SRY HMG box recognizes DNA by partial intercalation in the minor groove. Also involved in pre-mRNA splicing. Binds to the DNA consensus sequence 5'-[AT]AACAA[AT]-3'.<ref>PMID:11818535</ref> <ref>PMID:15170344</ref> <ref>PMID:16762365</ref> <ref>PMID:11563911</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hr/1hrz_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1hrz ConSurf].
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== Publication Abstract from PubMed ==
The solution structure of the specific complex between the high mobility group (HMG) domain of SRY (hSRY-HMG), the protein encoded by the human testis-determining gene, and its DNA target site in the promoter of the mullerian inhibitory substance gene has been determined by multidimensional NMR spectroscopy. hSRY-HMG has a twisted L shape that presents a concave surface (made up of three helices and the N- and C-terminal strands) to the DNA for sequence-specific recognition. Binding of hSRY-HMG to its specific target site occurs exclusively in the minor groove and induces a large conformational change in the DNA. The DNA in the complex has an overall 70 degrees-80 degrees bend and is helically unwound relative to classical A- and B-DNA. The structure of the complex reveals the origin of sequence-specific binding within the HMG-1/HMG-2 family and provides a framework for understanding the effects of point mutations that cause 46X,Y sex reversal at the atomic level.

Molecular basis of human 46X,Y sex reversal revealed from the three-dimensional solution structure of the human SRY-DNA complex.,Werner MH, Huth JR, Gronenborn AM, Clore GM Cell. 1995 Jun 2;81(5):705-14. PMID:7774012<ref>PMID:7774012</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1hrz" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Clore GM]]
[[Category: Gronenborn AM]]
[[Category: Huth JR]]
[[Category: Werner MH]]