6c24

Cryo-EM structure of PRC2 bound to cofactors AEBP2 and JARID2 in the Extended Active State

Loading... Status: waiting for Mol* initialization Structural highlights 6c24 is a 12 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.5Å Ligands: M3L Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease SUZ12_HUMAN A chromosomal aberration involving SUZ12 may be a cause of endometrial stromal tumors. Translocation t(7;17)(p15;q21) with JAZF1. The translocation generates the JAZF1-SUZ12 oncogene consisting of the N-terminus part of JAZF1 and the C-terminus part of SUZ12. It is frequently found in all cases of endometrial stromal tumors, except in endometrial stromal sarcomas, where it is rarer. Function SUZ12_HUMAN Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1 and CDKN2A. Publication Abstract from PubMed Transcriptionally repressive histone H3K27 methylation by PRC2 (Polycomb repressive complex 2) is essential for cellular differentiation and development. Here we report cryo-EM structures of human PRC2 in two distinct, active states, while in complex with its cofactors JARID2 and AEBP2. Both cofactors mimic the binding of histone H3 tails. JARID2, methylated by PRC2, mimics a methylated H3 tail to stimulate PRC2 activity, while AEBP2 interacts with the RBAP48 subunit mimicking an unmodified H3 tail. SUZ12 interacts with all other subunits within the assembly and thus contributes to the stability of the complex. Our analysis defines the complete architecture of a functionally relevant PRC2 and provides a structural framework to understand its regulation by cofactors, histone tails and RNA. Structures of human PRC2 with its cofactors AEBP2 and JARID2.,Kasinath V, Faini M, Poepsel S, Reif D, Feng XA, Stjepanovic G, Aebersold R, Nogales E Science. 2018 Jan 18. pii: science.aar5700. doi: 10.1126/science.aar5700. PMID:29348366 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone methyltransferase 3D structures Jumonji domain-containing protein 3D structures Polycomb complex proteins 3D structures Retinoblastoma-binding protein 3D structures

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