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Yorodumi- PDB-5u15: Crystal Structure of DH270.UCA3 (unliganded) from the DH270 Broad... -
+Open data
-Basic information
Entry | Database: PDB / ID: 5u15 | |||||||||
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Title | Crystal Structure of DH270.UCA3 (unliganded) from the DH270 Broadly Neutralizing N332-glycan Dependent Lineage | |||||||||
Components |
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Keywords | IMMUNE SYSTEM / FAB FRAGMENT / HIV-1 / ANTIBODY | |||||||||
Function / homology | Immunoglobulins / Immunoglobulin-like / Sandwich / Mainly Beta Function and homology information | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.26 Å | |||||||||
Authors | Fera, D. / Harrison, S.C. | |||||||||
Funding support | United States, 2items
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Citation | Journal: Sci Transl Med / Year: 2017 Title: Staged induction of HIV-1 glycan-dependent broadly neutralizing antibodies. Authors: Mattia Bonsignori / Edward F Kreider / Daniela Fera / R Ryan Meyerhoff / Todd Bradley / Kevin Wiehe / S Munir Alam / Baptiste Aussedat / William E Walkowicz / Kwan-Ki Hwang / Kevin O ...Authors: Mattia Bonsignori / Edward F Kreider / Daniela Fera / R Ryan Meyerhoff / Todd Bradley / Kevin Wiehe / S Munir Alam / Baptiste Aussedat / William E Walkowicz / Kwan-Ki Hwang / Kevin O Saunders / Ruijun Zhang / Morgan A Gladden / Anthony Monroe / Amit Kumar / Shi-Mao Xia / Melissa Cooper / Mark K Louder / Krisha McKee / Robert T Bailer / Brendan W Pier / Claudia A Jette / Garnett Kelsoe / Wilton B Williams / Lynn Morris / John Kappes / Kshitij Wagh / Gift Kamanga / Myron S Cohen / Peter T Hraber / David C Montefiori / Ashley Trama / Hua-Xin Liao / Thomas B Kepler / M Anthony Moody / Feng Gao / Samuel J Danishefsky / John R Mascola / George M Shaw / Beatrice H Hahn / Stephen C Harrison / Bette T Korber / Barton F Haynes / Abstract: A preventive HIV-1 vaccine should induce HIV-1-specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and ...A preventive HIV-1 vaccine should induce HIV-1-specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3-glycan bnAb. Two autologous neutralizing antibody lineages selected for virus escape mutations and consequently allowed initiation and affinity maturation of a V3-glycan bnAb lineage. The nucleotide substitution required to initiate the bnAb lineage occurred at a low-probability site for activation-induced cytidine deaminase activity. Cooperation of B cell lineages and an improbable mutation critical for bnAb activity defined the necessary events leading to breadth in this V3-glycan bnAb lineage. These findings may, in part, explain why initiation of V3-glycan bnAbs is rare, and suggest an immunization strategy for inducing similar V3-glycan bnAbs. | |||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 5u15.cif.gz | 333.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb5u15.ent.gz | 274.1 KB | Display | PDB format |
PDBx/mmJSON format | 5u15.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 5u15_validation.pdf.gz | 449.8 KB | Display | wwPDB validaton report |
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Full document | 5u15_full_validation.pdf.gz | 464.7 KB | Display | |
Data in XML | 5u15_validation.xml.gz | 33.3 KB | Display | |
Data in CIF | 5u15_validation.cif.gz | 47.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/u1/5u15 ftp://data.pdbj.org/pub/pdb/validation_reports/u1/5u15 | HTTPS FTP |
-Related structure data
Related structure data | 8507C 5tplC 5tppC 5tqaC 5trpC 5u0rSC 5u0uC C: citing same article (ref.) S: Starting model for refinement |
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Similar structure data |
-Links
-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:
NCS ensembles :
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-Components
#1: Antibody | Mass: 25779.795 Da / Num. of mol.: 2 / Fragment: FAB Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Plasmid: pVRC-8400 / Cell line (production host): HEK 293T / Production host: Homo sapiens (human) #2: Antibody | Mass: 22648.039 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK 293T / Production host: Homo sapiens (human) #3: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.62 Å3/Da / Density % sol: 53.07 % |
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Crystal grow | Temperature: 293 K / Method: vapor diffusion, hanging drop / pH: 5 Details: 20% PEG 4000, 100 mM Na acetate pH 5.0, 100 mM MgSO4 |
-Data collection
Diffraction | Mean temperature: 100 K |
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Diffraction source | Source: SYNCHROTRON / Site: APS / Beamline: 24-ID-E / Wavelength: 0.97925 Å |
Detector | Type: ADSC QUANTUM 315 / Detector: CCD / Date: Nov 20, 2014 |
Radiation | Monochromator: SINGLE CRYSTAL SI(220) SIDE BOUNCE / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97925 Å / Relative weight: 1 |
Reflection | Resolution: 2.26→48.214 Å / Num. obs: 46692 / % possible obs: 99.2 % / Redundancy: 3.1 % / Biso Wilson estimate: 43.99 Å2 / Rmerge(I) obs: 0.096 / Net I/σ(I): 7.2 |
Reflection shell | Resolution: 2.26→2.3 Å / Redundancy: 3 % / Rmerge(I) obs: 0.878 / % possible all: 99.9 |
-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 5U0R Resolution: 2.26→48.21 Å / SU ML: 0.3 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 26.88
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Solvent computation | Shrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso mean: 58.56 Å2 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Refinement step | Cycle: LAST / Resolution: 2.26→48.21 Å
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Refine LS restraints |
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Refine LS restraints NCS |
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LS refinement shell |
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Refinement TLS params. | Method: refined / Origin x: 4.9613 Å / Origin y: 55.8009 Å / Origin z: -39.057 Å
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Refinement TLS group | Selection details: ALL |