7yhq

CryoEM structure of Arabidopsis ROS1 in complex with a covalent-linked reaction intermediate at 3.9 Angstroms resolution

spinqualitylabelsall models 7yhq, resolution 3.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7yhq is a 3 chain structure with sequence from Arabidopsis thaliana and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.9Å Ligands: PED Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease SRY_HUMAN Defects in SRY are the cause of 46,XY sex reversal type 1 (SRXY1) [MIM: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. [:] [:] 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:400045. A condition in which male gonads develop in a genetic female (female to male sex reversal). Function 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'. 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). 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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