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基本情報
登録情報 | データベース: PDB / ID: 5an9 | |||||||||
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タイトル | Mechanism of eIF6 release from the nascent 60S ribosomal subunit | |||||||||
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![]() | TRANSLATION / RIBOSOMOPATHY / EFL1 / GTPASE / RIBOSOME BIOGENESIS | |||||||||
機能・相同性 | ![]() Recognition of DNA damage by PCNA-containing replication complex / Downregulation of ERBB2:ERBB3 signaling / L13a-mediated translational silencing of Ceruloplasmin expression / APC/C:Cdc20 mediated degradation of Cyclin B / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / APC-Cdc20 mediated degradation of Nek2A / SRP-dependent cotranslational protein targeting to membrane ...Recognition of DNA damage by PCNA-containing replication complex / Downregulation of ERBB2:ERBB3 signaling / L13a-mediated translational silencing of Ceruloplasmin expression / APC/C:Cdc20 mediated degradation of Cyclin B / Autodegradation of Cdh1 by Cdh1:APC/C / APC/C:Cdc20 mediated degradation of Securin / APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1 / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / APC-Cdc20 mediated degradation of Nek2A / SRP-dependent cotranslational protein targeting to membrane / Separation of Sister Chromatids / Senescence-Associated Secretory Phenotype (SASP) / Autodegradation of the E3 ubiquitin ligase COP1 / ABC-family proteins mediated transport / AUF1 (hnRNP D0) binds and destabilizes mRNA / Degradation of DVL / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Hedgehog ligand biogenesis / Hedgehog 'on' state / Translesion synthesis by POLK / Regulation of RAS by GAPs / MAPK6/MAPK4 signaling / UCH proteinases / Josephin domain DUBs / Ub-specific processing proteases / Metalloprotease DUBs / DNA Damage Recognition in GG-NER / Formation of Incision Complex in GG-NER / Gap-filling DNA repair synthesis and ligation in GG-NER / Formation of TC-NER Pre-Incision Complex / Dual incision in TC-NER / Gap-filling DNA repair synthesis and ligation in TC-NER / CDK-mediated phosphorylation and removal of Cdc6 / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Formation of a pool of free 40S subunits / GTP hydrolysis and joining of the 60S ribosomal subunit / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / E3 ubiquitin ligases ubiquitinate target proteins / Regulation of PTEN localization / Regulation of PTEN stability and activity / ER Quality Control Compartment (ERQC) / Interleukin-1 signaling / Peroxisomal protein import / Endosomal Sorting Complex Required For Transport (ESCRT) / Negative regulators of DDX58/IFIH1 signaling / Pexophagy / KEAP1-NFE2L2 pathway / Regulation of NF-kappa B signaling / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Regulation of pyruvate metabolism / Orc1 removal from chromatin / Cyclin D associated events in G1 / FBXL7 down-regulates AURKA during mitotic entry and in early mitosis / Neddylation / Iron uptake and transport / Antigen processing: Ubiquitination & Proteasome degradation / Aggrephagy / Regulation of necroptotic cell death / leukocyte chemotaxis / bone marrow development / inner cell mass cell proliferation / maturation of 5.8S rRNA / bone mineralization / ribosomal large subunit binding / preribosome, large subunit precursor / hematopoietic progenitor cell differentiation / ribosomal subunit export from nucleus / phagocytic vesicle / translation initiation factor activity / maturation of LSU-rRNA / extracellular matrix / lipid droplet / mitotic spindle organization / assembly of large subunit precursor of preribosome / cytosolic ribosome assembly / ribosomal large subunit biogenesis / spindle pole / modification-dependent protein catabolic process / rRNA processing / protein tag activity / ribosome biogenesis / ribosome binding / large ribosomal subunit rRNA binding / microtubule binding / cytosolic large ribosomal subunit / cytoplasmic translation / rRNA binding / ribosome / protein ubiquitination / structural constituent of ribosome / ribonucleoprotein complex / translation / mRNA binding / ubiquitin protein ligase binding / nucleolus / RNA binding / nucleoplasm / nucleus / cytosol 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: 3.3 Å | |||||||||
![]() | Weis, F. / Giudice, E. / Churcher, M. / Jin, L. / Hilcenko, C. / Wong, C.C. / Traynor, D. / Kay, R.R. / Warren, A.J. | |||||||||
![]() | ![]() タイトル: Mechanism of eIF6 release from the nascent 60S ribosomal subunit. 著者: Félix Weis / Emmanuel Giudice / Mark Churcher / Li Jin / Christine Hilcenko / Chi C Wong / David Traynor / Robert R Kay / Alan J Warren / ![]() ![]() 要旨: SBDS protein (deficient in the inherited leukemia-predisposition disorder Shwachman-Diamond syndrome) and the GTPase EFL1 (an EF-G homolog) activate nascent 60S ribosomal subunits for translation by ...SBDS protein (deficient in the inherited leukemia-predisposition disorder Shwachman-Diamond syndrome) and the GTPase EFL1 (an EF-G homolog) activate nascent 60S ribosomal subunits for translation by catalyzing eviction of the antiassociation factor eIF6 from nascent 60S ribosomal subunits. However, the mechanism is completely unknown. Here, we present cryo-EM structures of human SBDS and SBDS-EFL1 bound to Dictyostelium discoideum 60S ribosomal subunits with and without endogenous eIF6. SBDS assesses the integrity of the peptidyl (P) site, bridging uL16 (mutated in T-cell acute lymphoblastic leukemia) with uL11 at the P-stalk base and the sarcin-ricin loop. Upon EFL1 binding, SBDS is repositioned around helix 69, thus facilitating a conformational switch in EFL1 that displaces eIF6 by competing for an overlapping binding site on the 60S ribosomal subunit. Our data reveal the conserved mechanism of eIF6 release, which is corrupted in both inherited and sporadic leukemias. | |||||||||
履歴 |
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Remark 700 | SHEET DETERMINATION METHOD: DSSP THE SHEETS PRESENTED AS "EB" IN EACH CHAIN ON SHEET RECORDS BELOW ... SHEET DETERMINATION METHOD: DSSP THE SHEETS PRESENTED AS "EB" IN EACH CHAIN ON SHEET RECORDS BELOW IS ACTUALLY AN 5-STRANDED BARREL THIS IS REPRESENTED BY A 6-STRANDED SHEET IN WHICH THE FIRST AND LAST STRANDS ARE IDENTICAL. |
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構造の表示
ムービー |
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構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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PDBx/mmCIF形式 | ![]() | 1 MB | 表示 | ![]() |
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PDB形式 | ![]() | 790.3 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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要素
-60S RIBOSOMAL PROTEIN ... , 6種, 6分子 ABDEFG
#1: タンパク質 | 分子量: 45158.758 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) ![]() ![]() 株: HM2917 / 参照: UniProt: P34113 |
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#2: タンパク質 | 分子量: 21250.656 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) ![]() ![]() 株: HM2917 / 参照: UniProt: Q54XI5 |
#4: タンパク質 | 分子量: 17811.031 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) ![]() ![]() 株: HM2917 / 参照: UniProt: Q54J50 |
#5: タンパク質 | 分子量: 14567.147 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) ![]() ![]() 株: HM2917 / 参照: UniProt: Q54G86 |
#6: タンパク質 | 分子量: 24591.754 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) ![]() ![]() 株: HM2917 / 参照: UniProt: Q54J69 |
#7: タンパク質 | 分子量: 8334.771 Da / 分子数: 1 / Fragment: UNP RESIDUES 1-69 / 由来タイプ: 天然 由来: (天然) ![]() ![]() 株: HM2917 / 参照: UniProt: Q54VN6 |
-タンパク質 , 4種, 4分子 CHIJ
#3: タンパク質 | 分子量: 22434.189 Da / 分子数: 1 / Fragment: UNP RESIDUES 1-205 / 由来タイプ: 天然 由来: (天然) ![]() ![]() 株: HM2917 / 参照: UniProt: P22685 |
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#8: タンパク質 | 分子量: 6170.682 Da / 分子数: 1 / Fragment: UNP RESIDUES 77-128 / 由来タイプ: 天然 由来: (天然) ![]() ![]() 株: HM2917 / 参照: UniProt: P14794 |
#9: タンパク質 | 分子量: 24107.266 Da / 分子数: 1 / Fragment: UNP RESIDUES 1-224 / 由来タイプ: 天然 / 詳細: ENDOGENOUS PROTEIN 由来: (天然) ![]() ![]() 株: HM2917 / 参照: UniProt: Q551M2 |
#10: タンパク質 | 分子量: 28813.602 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
-RNA鎖 , 1種, 1分子 N
#11: RNA鎖 | 分子量: 1205997.750 Da / 分子数: 1 / 由来タイプ: 天然 由来: (天然) ![]() ![]() 株: HM2917 / 参照: GenBank: FR733594.1 |
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-詳細
配列の詳細 | RESIDUES 1-205 IN MODEL RESIDUES 1-69 IN THE MODEL NO UBIQUITIN IN MODEL RESIDUES 1-224 IN THE ...RESIDUES 1-205 IN MODEL RESIDUES 1-69 IN THE MODEL NO UBIQUITIN IN MODEL RESIDUES 1-224 IN THE MODEL FRAGMENTS A1221-A1270, C1356-C1602, A2392-U2700 AND A2925- C3480 IN THE MODEL |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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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 |
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試料調製
構成要素 | 名称: DICTYOSTELIUM 60S CARRYING ENDOGENOUS EIF6 WITH RECOMBINANT HUMAN SBDS タイプ: RIBOSOME |
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緩衝液 | 名称: 50 MM HEPES-KOH, 100 MM K(CH3COO), 10 MM MG(CH3COO)2, 6 MM BETA-MERCAPTOETHANOL pH: 7.5 詳細: 50 MM HEPES-KOH, 100 MM K(CH3COO), 10 MM MG(CH3COO)2, 6 MM BETA-MERCAPTOETHANOL |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | 詳細: HOLEY CARBON |
急速凍結 | 装置: FEI VITROBOT MARK III / 凍結剤: ETHANE 詳細: VITRIFICATION 1 -- CRYOGEN- ETHANE, HUMIDITY- 100, TEMPERATURE- 120, INSTRUMENT- FEI VITROBOT MARK III, METHOD- 6.5S BLOT, |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS / 日付: 2013年9月3日 |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 倍率(公称値): 59000 X / 倍率(補正後): 105263 X / 最大 デフォーカス(公称値): 2800 nm / 最小 デフォーカス(公称値): 2200 nm / Cs: 2.2 mm |
撮影 | 電子線照射量: 30 e/Å2 フィルム・検出器のモデル: FEI FALCON II (4k x 4k) |
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解析
EMソフトウェア |
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CTF補正 | 詳細: EACH PARTICLE | ||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||
3次元再構成 | 解像度: 3.3 Å / 粒子像の数: 43063 / ピクセルサイズ(公称値): 1.33 Å / ピクセルサイズ(実測値): 1.33 Å 詳細: SUBMISSION BASED ON EXPERIMENTAL DATA FROM EMDB EMD-3145. (DEPOSITION ID: 13748). 対称性のタイプ: POINT | ||||||||||||
原子モデル構築 | B value: 94.2 / プロトコル: OTHER / 空間: RECIPROCAL / Target criteria: FSCAVERAGE / 詳細: REFINEMENT PROTOCOL--CRYO-EM | ||||||||||||
精密化 | 最高解像度: 3.3 Å | ||||||||||||
精密化ステップ | サイクル: LAST / 最高解像度: 3.3 Å
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