+Open data
-Basic information
Entry | Database: PDB / ID: 8dso | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of cIAP1, BTK and BCCov | ||||||
Components |
| ||||||
Keywords | ONCOPROTEIN / E3 Ligase / PROTAC / Ternary Complex / BTK | ||||||
Function / homology | Function and homology information negative regulation of ripoptosome assembly involved in necroptotic process / regulation of cysteine-type endopeptidase activity / FBXO family protein binding / regulation of RIG-I signaling pathway / positive regulation of protein K48-linked ubiquitination / regulation of non-canonical NF-kappaB signal transduction / TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway / regulation of necroptotic process / regulation of B cell cytokine production / regulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway ...negative regulation of ripoptosome assembly involved in necroptotic process / regulation of cysteine-type endopeptidase activity / FBXO family protein binding / regulation of RIG-I signaling pathway / positive regulation of protein K48-linked ubiquitination / regulation of non-canonical NF-kappaB signal transduction / TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway / regulation of necroptotic process / regulation of B cell cytokine production / regulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway / proteoglycan catabolic process / monocyte proliferation / positive regulation of interleukin-17A production / positive regulation of protein K63-linked ubiquitination / regulation of B cell apoptotic process / eosinophil homeostasis / positive regulation of type III hypersensitivity / CD40 receptor complex / B cell affinity maturation / positive regulation of synoviocyte proliferation / histamine secretion by mast cell / neutrophil homeostasis / XY body / negative regulation of necroptotic process / cellular response to molecule of fungal origin / positive regulation of type I hypersensitivity / cellular response to interleukin-7 / MyD88 deficiency (TLR2/4) / regulation of reactive oxygen species metabolic process / positive regulation of protein monoubiquitination / TNFR1-induced proapoptotic signaling / MyD88-dependent toll-like receptor signaling pathway / IRAK4 deficiency (TLR2/4) / MyD88:MAL(TIRAP) cascade initiated on plasma membrane / RIPK1-mediated regulated necrosis / positive regulation of B cell differentiation / positive regulation of immunoglobulin production / positive regulation of NLRP3 inflammasome complex assembly / negative regulation of interleukin-10 production / phospholipase activator activity / B cell activation / regulation of toll-like receptor signaling pathway / regulation of innate immune response / Apoptotic cleavage of cellular proteins / negative regulation of B cell proliferation / regulation of cell differentiation / non-canonical NF-kappaB signal transduction / Fc-epsilon receptor signaling pathway / necroptotic process / mesoderm development / phosphatidylinositol-3,4,5-trisphosphate binding / phospholipase binding / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / RHO GTPases Activate WASPs and WAVEs / canonical NF-kappaB signal transduction / positive regulation of phagocytosis / positive regulation of B cell proliferation / cell maturation / response to cAMP / tumor necrosis factor-mediated signaling pathway / FCERI mediated Ca+2 mobilization / TICAM1, RIP1-mediated IKK complex recruitment / IKK complex recruitment mediated by RIP1 / Antigen activates B Cell Receptor (BCR) leading to generation of second messengers / TNFR1-induced NF-kappa-B signaling pathway / ubiquitin binding / positive regulation of protein ubiquitination / TNFR2 non-canonical NF-kB pathway / calcium-mediated signaling / placenta development / apoptotic signaling pathway / Regulation of TNFR1 signaling / FCGR3A-mediated phagocytosis / B cell receptor signaling pathway / non-specific protein-tyrosine kinase / non-membrane spanning protein tyrosine kinase activity / RING-type E3 ubiquitin transferase / NOD1/2 Signaling Pathway / Regulation of necroptotic cell death / cytoplasmic side of plasma membrane / G beta:gamma signalling through BTK / Regulation of actin dynamics for phagocytic cup formation / cellular response to reactive oxygen species / protein polyubiquitination / peptidyl-tyrosine phosphorylation / ubiquitin-protein transferase activity / positive regulation of interleukin-6 production / positive regulation of tumor necrosis factor production / G alpha (12/13) signalling events / ubiquitin protein ligase activity / DAP12 signaling / positive regulation of NF-kappaB transcription factor activity / T cell receptor signaling pathway / regulation of cell population proliferation / ER-Phagosome pathway / protein-folding chaperone binding / regulation of inflammatory response / transferase activity / cytoplasmic vesicle / G alpha (q) signalling events Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.334 Å | ||||||
Authors | Schiemer, J.S. / Calabrese, M.F. | ||||||
Funding support | 1items
| ||||||
Citation | Journal: Nat Commun / Year: 2023 Title: A covalent BTK ternary complex compatible with targeted protein degradation. Authors: Schiemer, J. / Maxwell, A. / Horst, R. / Liu, S. / Uccello, D.P. / Borzilleri, K. / Rajamohan, N. / Brown, M.F. / Calabrese, M.F. | ||||||
History |
|
-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
---|
-Downloads & links
-Download
PDBx/mmCIF format | 8dso.cif.gz | 92 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb8dso.ent.gz | 65.8 KB | Display | PDB format |
PDBx/mmJSON format | 8dso.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ds/8dso ftp://data.pdbj.org/pub/pdb/validation_reports/ds/8dso | HTTPS FTP |
---|
-Related structure data
Related structure data | 8dsfC 5p9jS C: citing same article (ref.) S: Starting model for refinement |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
| ||||||||
---|---|---|---|---|---|---|---|---|---|
1 |
| ||||||||
Unit cell |
|
-Components
#1: Protein | Mass: 32112.816 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BTK, AGMX1, ATK, BPK Production host: Spodoptera aff. frugiperda 2 RZ-2014 (butterflies/moths) References: UniProt: Q06187, non-specific protein-tyrosine kinase |
---|---|
#2: Protein | Mass: 11318.731 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: BIRC2, API1, MIHB, RNF48 / Production host: Escherichia coli (E. coli) References: UniProt: Q13490, RING-type E3 ubiquitin transferase |
#3: Chemical | ChemComp-TOO / ( |
#4: Chemical | ChemComp-ZN / |
#5: Water | ChemComp-HOH / |
Has ligand of interest | Y |
-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
---|
-Sample preparation
Crystal | Density Matthews: 3.99 Å3/Da / Density % sol: 70.22 % |
---|---|
Crystal grow | Temperature: 293 K / Method: vapor diffusion, sitting drop / pH: 9 Details: 0.1 M BTP pH 9, 4M potassium formate, and 2% PEG MME 2K |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
---|---|
Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å |
Detector | Type: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Apr 11, 2019 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 1 Å / Relative weight: 1 |
Reflection | Resolution: 2.334→110.29 Å / Num. obs: 17804 / % possible obs: 88.9 % / Redundancy: 9.9 % / Rpim(I) all: 0.113 / Net I/σ(I): 4.7 |
Reflection shell | Resolution: 2.337→2.734 Å / Num. unique obs: 890 / Rpim(I) all: 0.551 |
-Processing
Software |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5p9j Resolution: 2.334→110.29 Å / Cor.coef. Fo:Fc: 0.903 / Cor.coef. Fo:Fc free: 0.88 / SU R Cruickshank DPI: 0.456 / Cross valid method: THROUGHOUT / SU R Blow DPI: 0.446 / SU Rfree Blow DPI: 0.319 / SU Rfree Cruickshank DPI: 0.322
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 70.79 Å2
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine analyze | Luzzati coordinate error obs: 0.41 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.334→110.29 Å
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LS refinement shell | Resolution: 2.334→2.53 Å
|