7yhp
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | The entry | + | ==CryoEM structure of Arabidopsis ROS1 in complex with 5mC-dsDNA at 3.1 Angstroms resolution== |
| + | <StructureSection load='7yhp' size='340' side='right'caption='[[7yhp]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[7yhp]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YHP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YHP FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.1Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5CM:5-METHYL-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>5CM</scene>, <scene name='pdbligand=SF4:IRON/SULFUR+CLUSTER'>SF4</scene></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=7yhp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yhp OCA], [https://pdbe.org/7yhp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yhp RCSB], [https://www.ebi.ac.uk/pdbsum/7yhp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yhp 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> [https://www.uniprot.org/uniprot/ROS1_ARATH ROS1_ARATH] Bifunctional DNA glycosylase/lyase, which excises 5-methylcytosine (5-meC) and 5-hydroxymethylcytosine (5-hmeC), leaving an apyrimidinic (AP) site that is subsequently incised by the lyase activity (PubMed:25240767). Generates 3'-phosphor-alpha,beta-unsaturated aldehyde (3'-PUA) as a primary 5-meC excision intermediate (PubMed:25228464). Prevents DNA hypermethylation, specifically in the promoter of otherwise silenced loci. May be involved in DNA repair through its nicking activity on methylated DNA. Binds with similar affinity to both methylated and non-methylated DNA. Highly distributive behavior on DNA substrates containing multiple 5-meC residues. Involved with Pol IV in the remodeling of the 5S rDNA chromatin via DNA methylation modifications during the first days of development post-germination. Participates in UV-B induced- and oxidative DNA damage repair (PubMed:24155752).<ref>PMID:12526807</ref> <ref>PMID:16624880</ref> <ref>PMID:18845569</ref> <ref>PMID:19443451</ref> <ref>PMID:20489198</ref> <ref>PMID:24155752</ref> <ref>PMID:25228464</ref> <ref>PMID:25240767</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Active DNA demethylation plays a crucial role in eukaryotic gene imprinting and antagonizing DNA methylation. The plant-specific REPRESSOR OF SILENCING 1/DEMETER (ROS1/DME) family of enzymes directly excise 5-methyl-cytosine (5mC), representing an efficient DNA demethylation pathway distinct from that of animals. Here, we report the cryo-electron microscopy structures of an Arabidopsis ROS1 catalytic fragment in complex with substrate DNA, mismatch DNA and reaction intermediate, respectively. The substrate 5mC is flipped-out from the DNA duplex and subsequently recognized by the ROS1 base-binding pocket through hydrophobic and hydrogen-bonding interactions towards the 5-methyl group and Watson-Crick edge respectively, while the different protonation states of the bases determine the substrate preference for 5mC over T:G mismatch. Together with the structure of the reaction intermediate complex, our structural and biochemical studies revealed the molecular basis for substrate specificity, as well as the reaction mechanism underlying 5mC demethylation by the ROS1/DME family of plant-specific DNA demethylases. | ||
| - | + | Molecular basis of the plant ROS1-mediated active DNA demethylation.,Du X, Yang Z, Xie G, Wang C, Zhang L, Yan K, Yang M, Li S, Zhu JK, Du J Nat Plants. 2023 Feb;9(2):271-279. doi: 10.1038/s41477-022-01322-8. Epub 2023 Jan , 9. PMID:36624257<ref>PMID:36624257</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 7yhp" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Arabidopsis thaliana]] | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Du J]] | ||
| + | [[Category: Du X]] | ||
Current revision
CryoEM structure of Arabidopsis ROS1 in complex with 5mC-dsDNA at 3.1 Angstroms resolution
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