+
データを開く
-
基本情報
登録情報 | データベース: PDB / ID: 6sj7 | ||||||
---|---|---|---|---|---|---|---|
タイトル | Structure of the human DDB1-DDA1-DCAF15 E3 ubiquitin ligase bound to RBM39 and Indisulam | ||||||
![]() |
| ||||||
![]() | ONCOPROTEIN / DDB1 | ||||||
機能・相同性 | ![]() RS domain binding / regulation of natural killer cell activation / positive regulation by virus of viral protein levels in host cell / U1 snRNP binding / spindle assembly involved in female meiosis / regulation of mRNA splicing, via spliceosome / epigenetic programming in the zygotic pronuclei / UV-damage excision repair / biological process involved in interaction with symbiont / regulation of mitotic cell cycle phase transition ...RS domain binding / regulation of natural killer cell activation / positive regulation by virus of viral protein levels in host cell / U1 snRNP binding / spindle assembly involved in female meiosis / regulation of mRNA splicing, via spliceosome / epigenetic programming in the zygotic pronuclei / UV-damage excision repair / biological process involved in interaction with symbiont / regulation of mitotic cell cycle phase transition / WD40-repeat domain binding / Cul4A-RING E3 ubiquitin ligase complex / Cul4-RING E3 ubiquitin ligase complex / Cul4B-RING E3 ubiquitin ligase complex / ubiquitin ligase complex scaffold activity / small molecule binding / negative regulation of reproductive process / negative regulation of developmental process / cullin family protein binding / viral release from host cell / ectopic germ cell programmed cell death / RNA processing / positive regulation of viral genome replication / proteasomal protein catabolic process / immune system process / positive regulation of gluconeogenesis / mRNA Splicing - Major Pathway / RNA splicing / Recognition of DNA damage by PCNA-containing replication complex / DNA Damage Recognition in GG-NER / nucleotide-excision repair / Dual Incision in GG-NER / Transcription-Coupled Nucleotide Excision Repair (TC-NER) / Formation of TC-NER Pre-Incision Complex / Formation of Incision Complex in GG-NER / regulation of circadian rhythm / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / centriolar satellite / Wnt signaling pathway / mRNA processing / protein polyubiquitination / positive regulation of protein catabolic process / cellular response to UV / rhythmic process / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / site of double-strand break / Neddylation / microtubule cytoskeleton / ubiquitin-dependent protein catabolic process / protein-macromolecule adaptor activity / damaged DNA binding / proteasome-mediated ubiquitin-dependent protein catabolic process / chromosome, telomeric region / protein ubiquitination / nuclear speck / DNA repair / apoptotic process / DNA damage response / negative regulation of apoptotic process / protein-containing complex binding / nucleolus / protein-containing complex / extracellular space / DNA binding / RNA binding / extracellular exosome / nucleoplasm / metal ion binding / nucleus / cytoplasm 類似検索 - 分子機能 | ||||||
生物種 | ![]() | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.54 Å | ||||||
![]() | Srinivas, H. | ||||||
![]() | ![]() タイトル: Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex. 著者: Dirksen E Bussiere / Lili Xie / Honnappa Srinivas / Wei Shu / Ashley Burke / Celine Be / Junping Zhao / Adarsh Godbole / Dan King / Rajeshri G Karki / Viktor Hornak / Fangmin Xu / Jennifer ...著者: Dirksen E Bussiere / Lili Xie / Honnappa Srinivas / Wei Shu / Ashley Burke / Celine Be / Junping Zhao / Adarsh Godbole / Dan King / Rajeshri G Karki / Viktor Hornak / Fangmin Xu / Jennifer Cobb / Nathalie Carte / Andreas O Frank / Alexandra Frommlet / Patrick Graff / Mark Knapp / Aleem Fazal / Barun Okram / Songchun Jiang / Pierre-Yves Michellys / Rohan Beckwith / Hans Voshol / Christian Wiesmann / Jonathan M Solomon / Joshiawa Paulk / ![]() ![]() 要旨: The anticancer agent indisulam inhibits cell proliferation by causing degradation of RBM39, an essential mRNA splicing factor. Indisulam promotes an interaction between RBM39 and the DCAF15 E3 ligase ...The anticancer agent indisulam inhibits cell proliferation by causing degradation of RBM39, an essential mRNA splicing factor. Indisulam promotes an interaction between RBM39 and the DCAF15 E3 ligase substrate receptor, leading to RBM39 ubiquitination and proteasome-mediated degradation. To delineate the precise mechanism by which indisulam mediates the DCAF15-RBM39 interaction, we solved the DCAF15-DDB1-DDA1-indisulam-RBM39(RRM2) complex structure to a resolution of 2.3 Å. DCAF15 has a distinct topology that embraces the RBM39(RRM2) domain largely via non-polar interactions, and indisulam binds between DCAF15 and RBM39(RRM2), coordinating additional interactions between the two proteins. Studies with RBM39 point mutants and indisulam analogs validated the structural model and defined the RBM39 α-helical degron motif. The degron is found only in RBM23 and RBM39, and only these proteins were detectably downregulated in indisulam-treated HCT116 cells. This work further explains how indisulam induces RBM39 degradation and defines the challenge of harnessing DCAF15 to degrade additional targets. | ||||||
履歴 |
|
-
構造の表示
ムービー |
![]() |
---|---|
構造ビューア | 分子: ![]() ![]() |
-
ダウンロードとリンク
-
ダウンロード
PDBx/mmCIF形式 | ![]() | 254.3 KB | 表示 | ![]() |
---|---|---|---|---|
PDB形式 | ![]() | 189.8 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 823.2 KB | 表示 | ![]() |
---|---|---|---|---|
文書・詳細版 | ![]() | 837.7 KB | 表示 | |
XML形式データ | ![]() | 42.8 KB | 表示 | |
CIF形式データ | ![]() | 67.5 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
-
リンク
-
集合体
登録構造単位 | ![]()
|
---|---|
1 |
|
-
要素
#1: タンパク質 | 分子量: 66563.297 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q66K64 |
---|---|
#2: タンパク質 | 分子量: 127097.469 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q16531 |
#3: タンパク質 | 分子量: 9085.409 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
#4: タンパク質 | 分子量: 11724.102 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q9BW61 |
#5: 化合物 | ChemComp-EF6 / |
研究の焦点であるリガンドがあるか | Y |
Has protein modification | Y |
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-
試料調製
構成要素 |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
分子量 | 値: 0.21 MDa / 実験値: YES | ||||||||||||||||||||||||
由来(天然) |
| ||||||||||||||||||||||||
由来(組換発現) |
| ||||||||||||||||||||||||
緩衝液 | pH: 7.5 | ||||||||||||||||||||||||
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||||||
急速凍結 | 凍結剤: ETHANE |
-
電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
---|---|
顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 40 e/Å2 / 検出モード: COUNTING フィルム・検出器のモデル: GATAN K2 QUANTUM (4k x 4k) |
-
解析
CTF補正 | タイプ: NONE |
---|---|
3次元再構成 | 解像度: 3.54 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 380000 / 対称性のタイプ: POINT |