6uh5

Structural basis of COMPASS eCM recognition of the H2Bub nucleosome

Loading... Status: waiting for Mol* initialization Structural highlights 6uh5 is a 19 chain structure with sequence from African clawed frog, Candida sphaerica and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: SAM, ZN Gene: hist1h3g, H3l (African clawed frog), KLLA0_A08800g (Candida sphaerica), UBB (HUMAN), KLLA0_D07260g (Candida sphaerica), KLLA0_C10945g (Candida sphaerica), KLLA0_E03521g (Candida sphaerica), hist1h2aj, LOC494591, XELAEV_18003602mg (African clawed frog), XELAEV_18032686mg (African clawed frog), KLLA0_E24487g (Candida sphaerica), SET1, KLLA0F24134g (Candida sphaerica) Activity: Histone-lysine N-methyltransferase, with EC number 2.1.1.43 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [SET1_KLULA] Catalytic component of the COMPASS (Set1C) complex that specifically mono-, di- and trimethylates histone H3 to form H3K4me1/2/3, which subsequently plays a role in telomere length maintenance and transcription elongation regulation. [H4_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Publication Abstract from PubMed The COMPASS (complex of proteins associated with Set1) complex represents the prototype of the SET1/MLL family of methyltransferases that controls gene transcription by H3K4 methylation (H3K4me). Although H2B monoubiquitination (H2Bub) is well known as a prerequisite histone mark for COMPASS activity, how H2Bub activates COMPASS remains unclear. Here, we report the cryoelectron microscopy (cryo-EM) structures of an extended COMPASS catalytic module (CM) bound to the H2Bub and free nucleosome. The COMPASS CM clamps onto the nucleosome disk-face via an extensive interface to capture the flexible H3 N-terminal tail. The interface also sandwiches a critical Set1 arginine-rich motif (ARM) that autoinhibits COMPASS. Unexpectedly, without enhancing COMPASS-nucleosome interaction, H2Bub activates the enzymatic assembly by packing against Swd1 and alleviating the inhibitory effect of the Set1 ARM upon fastening it to the acidic patch. By delineating the spatial configuration of the COMPASS-H2Bub-nucleosome assembly, our studies establish the structural framework for understanding the long-studied H2Bub-H3K4me histone modification crosstalk. Structural Basis of H2B Ubiquitination-Dependent H3K4 Methylation by COMPASS.,Hsu PL, Shi H, Leonen C, Kang J, Chatterjee C, Zheng N Mol Cell. 2019 Oct 29. pii: S1097-2765(19)30791-9. doi:, 10.1016/j.molcel.2019.10.013. PMID:31733991 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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