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-Structure paper
タイトル | Structural basis of paralog-specific KDM2A/B nucleosome recognition. |
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ジャーナル・号・ページ | Nat Chem Biol, Vol. 19, Issue 5, Page 624-632, Year 2023 |
掲載日 | 2023年2月16日 |
著者 | Cathy J Spangler / Aleksandra Skrajna / Caroline A Foley / Anh Nguyen / Gabrielle R Budziszewski / Dalal N Azzam / Eyla C Arteaga / Holly C Simmons / Charlotte B Smith / Nathaniel A Wesley / Emily M Wilkerson / Jeanne-Marie E McPherson / Dmitri Kireev / Lindsey I James / Stephen V Frye / Dennis Goldfarb / Robert K McGinty / |
PubMed 要旨 | The nucleosome acidic patch is a major interaction hub for chromatin, providing a platform for enzymes to dock and orient for nucleosome-targeted activities. To define the molecular basis of acidic ...The nucleosome acidic patch is a major interaction hub for chromatin, providing a platform for enzymes to dock and orient for nucleosome-targeted activities. To define the molecular basis of acidic patch recognition proteome wide, we performed an amino acid resolution acidic patch interactome screen. We discovered that the histone H3 lysine 36 (H3K36) demethylase KDM2A, but not its closely related paralog, KDM2B, requires the acidic patch for nucleosome binding. Despite fundamental roles in transcriptional repression in health and disease, the molecular mechanisms governing nucleosome substrate specificity of KDM2A/B, or any related JumonjiC (JmjC) domain lysine demethylase, remain unclear. We used a covalent conjugate between H3K36 and a demethylase inhibitor to solve cryogenic electron microscopy structures of KDM2A and KDM2B trapped in action on a nucleosome substrate. Our structures show that KDM2-nucleosome binding is paralog specific and facilitated by dynamic nucleosomal DNA unwrapping and histone charge shielding that mobilize the H3K36 sequence for demethylation. |
リンク | Nat Chem Biol / PubMed:36797403 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.98 - 3.6 Å |
構造データ | EMDB-26809, PDB-7uv9: EMDB-26810: KDM2B-nucleosome complex stabilized by H3K36C-UNC8015 covalent conjugate PDB-7uva: |
化合物 | ChemComp-OH0: ChemComp-FE: ChemComp-HOH: |
由来 |
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キーワード | GENE REGULATION/DNA / chromatin nucleosome lysine demethylase JmjC protein / GENE REGULATION-DNA complex / GENE REGULATION (遺伝子発現の調節) / demethylase / histone (ヒストン) / inhibitor (酵素阻害剤) |