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Open data
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Basic information
Entry | Database: PDB / ID: 7kfz | ||||||
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Title | Structure of a ternary KRas(G13D)-SOS complex | ||||||
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![]() | HYDROLASE/SIGNALING PROTEIN / Ras / Sos / ![]() | ||||||
Function / homology | ![]() midbrain morphogenesis / regulation of pro-B cell differentiation / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Liu, C. / Moghadamchargari, Z. / Laganowsky, A. / Zhao, M. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Molecular assemblies of the catalytic domain of SOS with KRas and oncogenic mutants. Authors: Zahra Moghadamchargari / Mehdi Shirzadeh / Chang Liu / Samantha Schrecke / Charles Packianathan / David H Russell / Minglei Zhao / Arthur Laganowsky / ![]() Abstract: Ras is regulated by a specific guanine nucleotide exchange factor Son of Sevenless (SOS), which facilitates the exchange of inactive, GDP-bound Ras with GTP. The catalytic activity of SOS is also ...Ras is regulated by a specific guanine nucleotide exchange factor Son of Sevenless (SOS), which facilitates the exchange of inactive, GDP-bound Ras with GTP. The catalytic activity of SOS is also allosterically modulated by an active Ras (Ras-GTP). However, it remains poorly understood how oncogenic Ras mutants interact with SOS and modulate its activity. Here, native ion mobility-mass spectrometry is employed to monitor the assembly of the catalytic domain of SOS (SOS) with KRas and three cancer-associated mutants (G12C, G13D, and Q61H), leading to the discovery of different molecular assemblies and distinct conformers of SOS engaging KRas. We also find KRas exhibits high affinity for SOS and is a potent allosteric modulator of its activity. A structure of the KRas•SOS complex was determined using cryogenic electron microscopy providing insight into the enhanced affinity of the mutant protein. In addition, we find that KRas-GTP can allosterically increase the nucleotide exchange rate of KRas at the active site more than twofold compared to KRas-GTP. Furthermore, small-molecule Ras•SOS disruptors fail to dissociate KRas•SOS complexes, underscoring the need for more potent disruptors. Taken together, a better understanding of the interaction between oncogenic Ras mutants and SOS will provide avenues for improved therapeutic interventions. | ||||||
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Structure visualization
Movie |
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Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 159.3 KB | Display | ![]() |
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PDB format | ![]() | 121.4 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 22857MC M: map data used to model this data C: citing same article ( |
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Similar structure data | |
EM raw data | ![]() Data size: 3.7 TB Data #1: Unaligned raw movie of SOS-KRas (G13D) complex [micrographs - multiframe]) |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 19386.848 Da / Num. of mol.: 2 / Mutation: G13D Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() ![]() #2: Protein | | Mass: 57449.691 Da / Num. of mol.: 1 / Fragment: UNP residues 564-1049 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() #3: Chemical | ChemComp-GNP / | ![]() #4: Chemical | ChemComp-MG / | Has ligand of interest | N | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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Sample preparation
Component | Name: A ternary complex of KRas(G13D) and SOScat / Type: COMPLEX / Entity ID: #1-#2 / Source: RECOMBINANT |
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Molecular weight | Value: 0.0967 MDa / Experimental value: YES |
Source (natural) | Organism: ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 8.6 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
Vitrification![]() | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 281 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() ![]() |
Image recording | Electron dose: 65 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of real images: 5202 |
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Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||||||||||
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EM software |
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CTF correction![]() | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 5749548 | ||||||||||||||||||||||||||||||||
Symmetry | Point symmetry![]() | ||||||||||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 3.47 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 1021288 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | B value: 50 / Protocol: AB INITIO MODEL / Space: REAL | ||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 1XD2 Accession code: 1XD2 / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||||||||||
Refine LS restraints |
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