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Open data
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Basic information
Entry | Database: PDB / ID: 6cw1 | ||||||
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Title | Crystal structure of Neurexin-1 alpha ectodomain fragment, L2-L3 | ||||||
![]() | Neurexin-1 | ||||||
![]() | CELL ADHESION / LNS domain / Beta-Sandwich / Synapse | ||||||
Function / homology | ![]() neuroligin family protein binding / cell projection / presynaptic membrane / cell adhesion / metal ion binding Similarity search - Function | ||||||
Biological species | ![]() ![]() | ||||||
Method | ![]() ![]() ![]() ![]() | ||||||
![]() | Misra, A. / Rudenko, G. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structural Plasticity of Neurexin 1α: Implications for its Role as Synaptic Organizer. Authors: Jianfang Liu / Anurag Misra / M V V V Sekhar Reddy / Mark Andrew White / Gang Ren / Gabby Rudenko / ![]() Abstract: α-Neurexins are synaptic organizing molecules implicated in neuropsychiatric disorders. They bind and arrange an array of different partners in the synaptic cleft. The extracellular region of ...α-Neurexins are synaptic organizing molecules implicated in neuropsychiatric disorders. They bind and arrange an array of different partners in the synaptic cleft. The extracellular region of neurexin 1α (n1α) contains six LNS domains (L1-L6) interspersed by three Egf-like repeats. N1α must encode highly evolved structure-function relationships in order to fit into the narrow confines of the synaptic cleft, and also recruit its large, membrane-bound partners. Internal molecular flexibility could provide a solution; however, it is challenging to delineate because currently no structural methods permit high-resolution structure determination of large, flexible, multi-domain protein molecules. To investigate the structural plasticity of n1α, in particular the conformation of domains that carry validated binding sites for different protein partners, we used a panel of structural techniques. Individual particle electron tomography revealed that the N-terminally and C-terminally tethered domains, L1 and L6, have a surprisingly limited range of conformational freedom with respect to the linear central core containing L2 through L5. A 2.8-Å crystal structure revealed an unexpected arrangement of the L2 and L3 domains. Small-angle X-ray scattering and electron tomography indicated that incorporation of the alternative splice insert SS6 relieves the restricted conformational freedom between L5 and L6, suggesting that SS6 may work as a molecular toggle. The architecture of n1α thus encodes a combination of rigid and flexibly tethered domains that are uniquely poised to work together to promote its organizing function in the synaptic cleft, and may permit allosterically regulated and/or concerted protein partner binding. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 302.6 KB | Display | ![]() |
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PDB format | ![]() | 245.1 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 443 KB | Display | ![]() |
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Full document | ![]() | 452.8 KB | Display | |
Data in XML | ![]() | 27.8 KB | Display | |
Data in CIF | ![]() | 37.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7639C ![]() 7640C ![]() 7641C ![]() 7642C ![]() 7643C ![]() 7644C ![]() 7645C ![]() 7646C ![]() 7647C ![]() 7648C ![]() 7649C ![]() 7650C ![]() 7651C ![]() 7652C ![]() 7653C ![]() 7654C ![]() 7655C ![]() 7656C ![]() 7657C ![]() 7658C ![]() 7659C ![]() 7660C ![]() 7661C ![]() 7662C ![]() 7663C ![]() 7664C ![]() 7665C ![]() 7666C ![]() 7667C ![]() 7668C ![]() 7669C ![]() 7670C ![]() 7671C ![]() 7672C ![]() 7673C ![]() 7674C ![]() 7675C ![]() 7676C ![]() 7677C ![]() 7678C ![]() 7679C ![]() 7680C ![]() 7681C ![]() 7682C ![]() 7683C ![]() 7684C ![]() 7685C ![]() 7686C ![]() 7687C ![]() 7688C ![]() 7689C ![]() 7690C ![]() 7691C ![]() 7692C ![]() 7693C ![]() 7694C ![]() 7695C ![]() 7696C ![]() 7697C ![]() 7698C ![]() 7699C ![]() 7700C ![]() 7701C ![]() 7702C ![]() 7703C ![]() 7704C ![]() 7705C ![]() 7706C ![]() 7707C ![]() 7708C ![]() 7709C ![]() 7710C ![]() 7711C ![]() 7712C ![]() 7713C ![]() 7714C ![]() 7715C ![]() 7716C ![]() 7717C ![]() 7718C ![]() 7719C ![]() 7720C ![]() 7721C ![]() 7722C ![]() 7723C ![]() 7724C ![]() 7725C ![]() 7726C ![]() 7727C ![]() 7728C ![]() 7729C ![]() 7730C ![]() 7731C ![]() 7732C ![]() 7733C ![]() 7734C ![]() 7735C ![]() 7736C ![]() 7737C ![]() 7738C ![]() 7739C ![]() 7740C ![]() 7741C ![]() 7742C ![]() 7743C ![]() 7744C ![]() 7745C ![]() 7746C ![]() 7747C ![]() 7748C ![]() 7749C ![]() 7750C ![]() 7751C ![]() 7752C ![]() 7753C ![]() 7754C ![]() 7755C ![]() 7756C ![]() 7757C ![]() 7758C ![]() 7759C ![]() 7760C ![]() 7761C ![]() 7762C ![]() 7763C ![]() 7764C ![]() 7765C ![]() 7766C ![]() 7767C ![]() 7768C ![]() 3qcwS S: Starting model for refinement C: citing same article ( |
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Similar structure data |
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Assembly
Deposited unit | ![]()
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2 | ![]()
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Unit cell |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments: Component-ID: _ / Ens-ID: 1 / Beg auth comp-ID: LYS / Beg label comp-ID: LYS / End auth comp-ID: THR / End label comp-ID: THR / Refine code: _ / Auth seq-ID: 279 - 672 / Label seq-ID: 22 - 400
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Components
#1: Protein | Mass: 44517.121 Da / Num. of mol.: 2 / Fragment: Alpha fragment L2-L3, residues 258-674 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() #2: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: ![]() |
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Sample preparation
Crystal | Density Matthews: 3.45 Å3/Da / Density % sol: 64.39 % / Mosaicity: 1.742 ° |
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Crystal grow | Temperature: 298 K / Method: vapor diffusion, hanging drop / pH: 8 / Details: 0.9 M NaCITRATE, 0.1 M TRIS PH 8.0, 5 MM CACL2 |
-Data collection
Diffraction | Mean temperature: 100 K | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Diffraction source | Source: ![]() ![]() ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Detector | Type: MARMOSAIC 300 mm CCD / Detector: CCD / Date: Mar 21, 2008 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Radiation wavelength | Wavelength: 1.10208 Å / Relative weight: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection | Resolution: 2.84→50.01 Å / Num. obs: 28540 / % possible obs: 98.4 % / Redundancy: 3.4 % / Rmerge(I) obs: 0.091 / Rpim(I) all: 0.058 / Rrim(I) all: 0.108 / Χ2: 1.469 / Net I/σ(I): 15.2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reflection shell | Diffraction-ID: 1
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-Phasing
Phasing | Method: ![]() |
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Processing
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Refinement | Method to determine structure: ![]() Starting model: 3QCW Resolution: 2.84→50.01 Å / Cor.coef. Fo:Fc: 0.923 / Cor.coef. Fo:Fc free: 0.889 / SU B: 35.561 / SU ML: 0.307 / SU R Cruickshank DPI: 0.7583 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.758 / ESU R Free: 0.341 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 138.21 Å2 / Biso mean: 52.259 Å2 / Biso min: 24.48 Å2
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Refinement step | Cycle: final / Resolution: 2.84→50.01 Å
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Refine LS restraints |
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Refine LS restraints NCS | Ens-ID: 1 / Number: 22294 / Refine-ID: X-RAY DIFFRACTION / Type: interatomic distance / Rms dev position: 0.1 Å / Weight position: 0.05
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LS refinement shell | Resolution: 2.837→2.911 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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Refinement TLS params. | Method: refined / Refine-ID: X-RAY DIFFRACTION
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Refinement TLS group |
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