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- SASDBU3: RNF8 (L451D mutant) complexed with Ubc13 (C87K, K92A mutant) and ... -
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Open data
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Basic information
Entry | Database: SASBDB / ID: SASDBU3 |
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![]() | RNF8 (L451D mutant) complexed with Ubc13 (C87K, K92A mutant) and Mms2: conjugated to Ubiquitin
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Function / homology | ![]() error-free postreplication DNA repair / : / UBC13-MMS2 complex / ubiquitin conjugating enzyme complex / sperm DNA condensation / ubiquitin-protein transferase activator activity / positive regulation of protein K63-linked ubiquitination / DNA double-strand break processing / protein K6-linked ubiquitination / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function |
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![]() | ![]() Title: RNF8 E3 Ubiquitin Ligase Stimulates Ubc13 E2 Conjugating Activity That Is Essential for DNA Double Strand Break Signaling and BRCA1 Tumor Suppressor Recruitment. Authors: Curtis D Hodge / Ismail H Ismail / Ross A Edwards / Greg L Hura / Andrew T Xiao / John A Tainer / Michael J Hendzel / J N Mark Glover / ![]() ![]() ![]() Abstract: DNA double strand break (DSB) responses depend on the sequential actions of the E3 ubiquitin ligases RNF8 and RNF168 plus E2 ubiquitin-conjugating enzyme Ubc13 to specifically generate histone Lys-63- ...DNA double strand break (DSB) responses depend on the sequential actions of the E3 ubiquitin ligases RNF8 and RNF168 plus E2 ubiquitin-conjugating enzyme Ubc13 to specifically generate histone Lys-63-linked ubiquitin chains in DSB signaling. Here, we defined the activated RNF8-Ubc13∼ubiquitin complex by x-ray crystallography and its functional solution conformations by x-ray scattering, as tested by separation-of-function mutations imaged in cells by immunofluorescence. The collective results show that the RING E3 RNF8 targets E2 Ubc13 to DSB sites and plays a critical role in damage signaling by stimulating polyubiquitination through modulating conformations of ubiquitin covalently linked to the Ubc13 active site. Structure-guided separation-of-function mutations show that the RNF8 E2 stimulating activity is essential for DSB signaling in mammalian cells and is necessary for downstream recruitment of 53BP1 and BRCA1. Chromatin-targeted RNF168 rescues 53BP1 recruitment involved in non-homologous end joining but not BRCA1 recruitment for homologous recombination. These findings suggest an allosteric approach to targeting the ubiquitin-docking cleft at the E2-E3 interface for possible interventions in cancer and chronic inflammation, and moreover, they establish an independent RNF8 role in BRCA1 recruitment. |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
-Data source
SASBDB page | ![]() |
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-Related structure data
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External links
Related items in Molecule of the Month |
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-Models
Model #476 | ![]() Type: mix / Software: MES-FoXS / Radius of dummy atoms: 1.90 A ![]() |
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Model #477 | ![]() Type: mix / Software: MES-FoXS / Radius of dummy atoms: 1.90 A ![]() |
Model #478 | ![]() Type: mix / Software: MES-FoXS / Radius of dummy atoms: 1.90 A ![]() |
Model #479 | ![]() Type: mix / Software: MES-FoXS / Radius of dummy atoms: 1.90 A ![]() |
Model #480 | ![]() Type: mix / Software: MES-FoXS / Radius of dummy atoms: 1.90 A ![]() |
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Sample
![]() | Name: RNF8 (L451D mutant) complexed with Ubc13 (C87K, K92A mutant) and Mms2: conjugated to Ubiquitin Entity id: 305 / 306 / 307 / 308 |
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Buffer | Name: HEPES![]() |
Entity #305 | Name: Ubc13 - C87K, K92A / Type: protein Description: Ubiquitin-conjugating enzyme E2 N double mutant (C87K, K92A) Formula weight: 17.89 / Num. of mol.: 2 / Source: Homo sapiens / References: UniProt: P61088 Sequence: GPLGSPEFMA GLPRRIIKET QRLLAEPVPG IKAEPDESNA RYFHVVIAGP QDSPFEGGTF KLELFLPEEY PMAAPKVRFM TKIYHPNVDK LGRIKLDILA DKWSPALQIR TVLLSIQALL SAPNPDDPLA NDVAEQWKTN EAQAIETARA WTRLYAMNNI |
Entity #306 | Name: UBC / Type: protein / Description: Polyubiquitin-C / Formula weight: 8.565 / Num. of mol.: 2 / Source: Homo sapiens / References: UniProt: P0CG48 Sequence: MQIFVKTLTG KTITLEVEPS DTIENVKAKI QDKEGIPPDQ QRLIFAGKQL EDGRTLSDYN IQKESTLHLV LRLRGG |
Entity #307 | Name: Mms2 (UBE2V2) / Type: protein / Description: Ubiquitin-conjugating enzyme E2 variant 2 / Formula weight: 17.147 / Num. of mol.: 2 / Source: Homo sapiens / References: UniProt: Q15819 Sequence: GPLGSPEFMA VSTGVKVPRN FRLLEELEEG QKGVGDGTVS WGLEDDEDMT LTRWTGMIIG PPRTNYENRI YSLKVECGPK YPEAPPSVRF VTKINMNGIN NSSGMVDARS IPVLAKWQNS YSIKVVLQEL RRLMMSKENM KLPQPPEGQT YNN |
Entity #308 | Name: RNF8 L451D / Type: protein Description: E3 ubiquitin-protein ligase RNF8 mutant (L451D) Formula weight: 17.62 / Num. of mol.: 2 / Source: Homo sapiens / References: UniProt: O76064 Sequence: GPLGSPEFQE HWALMEELNR SKKDFEAIIQ AKNKELEQTK EEKEKMQAQK EEVLSHMNDV LENELQCIIC SEYFIEAVTL NCAHSFCSYC INEWMKRKIE CPICRKDIKS KTYSDVLDNC INKMVNNLSS EVKERRIVLI RERKAKRLF |
-Experimental information
Beam | Instrument name: Advanced Light Source (ALS) 12.3.1 (SIBYLS) City: Berkeley, CA / 国: USA ![]() ![]() | |||||||||||||||||||||||||||
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Detector | Name: Pilatus 2M | |||||||||||||||||||||||||||
Scan |
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Distance distribution function P(R) |
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Result |
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