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Yorodumi- EMDB-9294: Germline VRC01 antibody recognition of a modified clade C HIV-1 e... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-9294 | |||||||||
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Title | Germline VRC01 antibody recognition of a modified clade C HIV-1 envelope trimer, 3 Fabs bound, sharpened map | |||||||||
Map data | Germline VRC01 antibody recognition of a modified clade C HIV-1 envelope trimer, 3 Fabs bound | |||||||||
Sample |
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Function / homology | Function and homology information immunoglobulin complex / immunoglobulin mediated immune response / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / antigen binding / clathrin-dependent endocytosis of virus by host cell / blood microparticle / viral protein processing ...immunoglobulin complex / immunoglobulin mediated immune response / positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / positive regulation of establishment of T cell polarity / host cell endosome membrane / antigen binding / clathrin-dependent endocytosis of virus by host cell / blood microparticle / viral protein processing / immune response / fusion of virus membrane with host plasma membrane / virus-mediated perturbation of host defense response / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / apoptotic process / host cell plasma membrane / structural molecule activity / virion membrane / extracellular space / plasma membrane Similarity search - Function | |||||||||
Biological species | Human immunodeficiency virus 1 / Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.8 Å | |||||||||
Authors | Borst AJ / Weidle CE / Gray MD / Frenz B / Snijder J / Joyce MG / Georgiev IS / Stewart-Jones GBE / Kwong PD / McGuire AT ...Borst AJ / Weidle CE / Gray MD / Frenz B / Snijder J / Joyce MG / Georgiev IS / Stewart-Jones GBE / Kwong PD / McGuire AT / DiMaio F / Stamatatos L / Pancera M / Veesler D | |||||||||
Funding support | United States, 1 items
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Citation | Journal: Elife / Year: 2018 Title: Germline VRC01 antibody recognition of a modified clade C HIV-1 envelope trimer and a glycosylated HIV-1 gp120 core. Authors: Andrew J Borst / Connor E Weidle / Matthew D Gray / Brandon Frenz / Joost Snijder / M Gordon Joyce / Ivelin S Georgiev / Guillaume Be Stewart-Jones / Peter D Kwong / Andrew T McGuire / Frank ...Authors: Andrew J Borst / Connor E Weidle / Matthew D Gray / Brandon Frenz / Joost Snijder / M Gordon Joyce / Ivelin S Georgiev / Guillaume Be Stewart-Jones / Peter D Kwong / Andrew T McGuire / Frank DiMaio / Leonidas Stamatatos / Marie Pancera / David Veesler / Abstract: VRC01 broadly neutralizing antibodies (bnAbs) target the CD4-binding site (CD4) of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein (Env). Unlike mature antibodies, corresponding ...VRC01 broadly neutralizing antibodies (bnAbs) target the CD4-binding site (CD4) of the human immunodeficiency virus-1 (HIV-1) envelope glycoprotein (Env). Unlike mature antibodies, corresponding VRC01 germline precursors poorly bind to Env. Immunogen design has mostly relied on glycan removal from trimeric Env constructs and has had limited success in eliciting mature VRC01 bnAbs. To better understand elicitation of such bnAbs, we characterized the inferred germline precursor of VRC01 in complex with a modified trimeric 426c Env by cryo-electron microscopy and a 426c gp120 core by X-ray crystallography, biolayer interferometry, immunoprecipitation, and glycoproteomics. Our results show VRC01 germline antibodies interacted with a wild-type 426c core lacking variable loops 1-3 in the presence and absence of a glycan at position Asn276, with the latter form binding with higher affinity than the former. Interactions in the presence of an Asn276 oligosaccharide could be enhanced upon carbohydrate shortening, which should be considered for immunogen design. | |||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_9294.map.gz | 88.9 MB | EMDB map data format | |
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Header (meta data) | emd-9294-v30.xml emd-9294.xml | 15.3 KB 15.3 KB | Display Display | EMDB header |
Images | emd_9294.png | 58.4 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-9294 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9294 | HTTPS FTP |
-Validation report
Summary document | emd_9294_validation.pdf.gz | 339 KB | Display | EMDB validaton report |
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Full document | emd_9294_full_validation.pdf.gz | 338.5 KB | Display | |
Data in XML | emd_9294_validation.xml.gz | 6.4 KB | Display | |
Data in CIF | emd_9294_validation.cif.gz | 7.3 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9294 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9294 | HTTPS FTP |
-Related structure data
Related structure data | 6myyMC 9295C 9303C 9304C 6mftC 6mzjC C: citing same article (ref.) M: atomic model generated by this map |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_9294.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Germline VRC01 antibody recognition of a modified clade C HIV-1 envelope trimer, 3 Fabs bound | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.36 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Sample components
-Entire : 426c DS-SOSIP D3
Entire | Name: 426c DS-SOSIP D3 |
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Components |
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-Supramolecule #1: 426c DS-SOSIP D3
Supramolecule | Name: 426c DS-SOSIP D3 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#3 |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Recombinant expression | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 450 KDa |
-Macromolecule #1: 426c DS-SOSIP D3
Macromolecule | Name: 426c DS-SOSIP D3 / type: protein_or_peptide / ID: 1 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Human immunodeficiency virus 1 |
Molecular weight | Theoretical: 70.243812 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: AENLWVTVYY GVPVWKEAKT TLFCASDAKA YEKEVHNVWA THACVPTDPN PQEVVLENVT ENFNMWKNDM VDQMQEDVIS IWDQSLKPC VKLTPLCVTL NCTNVNVTSN STNVNSSSTD NTTLGEIKNC SFDITTEIRD KTRKEYALFY RLDIVPLDNS S NPNSSNTY ...String: AENLWVTVYY GVPVWKEAKT TLFCASDAKA YEKEVHNVWA THACVPTDPN PQEVVLENVT ENFNMWKNDM VDQMQEDVIS IWDQSLKPC VKLTPLCVTL NCTNVNVTSN STNVNSSSTD NTTLGEIKNC SFDITTEIRD KTRKEYALFY RLDIVPLDNS S NPNSSNTY RLINCNTSTC TQACPKVTFD PIPIHYCAPA GYAILKCNNK TFNGKGPCNN VSTVQCTHGI KPVVSTQLLL NG SLAEEEI VIRSKNLADN AKIIIVQLNK SVEIVCTRPN NNTRRSIRIG PGQTFYATDI IGDIRQAYCN ISGRNWSEAV NQV KKKLKE HFPHKNISFQ SSSGGDLEIT THSFNCGGEF FYCNTSGLFN DTISNATIML PCRIKQIINM WQEVGKCIYA PPIK GNITC KSDITGLLLL RDGCNTANNA EIFRPGGGDM RDNWRSELYK YKVVKIEPLG VAPTRCKRRV VGRRRRRRAV GIGAV FLGF LGAAGSTMGA ASMTLTVQAR NLLSGIVQQQ SNLLRAPEAQ QHLLKLTVWG IKQLQARVLA VERYLRDQQL LGIWGC SGK LICCTNVPWN SSWSNRNLSE IWDNMTWLQW DKEISNYTQI IYGLLEESQN QQEKNEQDLL ALD |
-Macromolecule #2: VRC01GL light chain
Macromolecule | Name: VRC01GL light chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 25.008906 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MGWSCIILFL VATATGVHSE IVLTQSPATL SLSPGERATL SCRASQSVSS YLAWYQQKPG QAPRLLIYDA SNRATGIPAR FSGSGSGTD FTLTISSLEP EDFAVYYCQQ YEFFGQGTKL EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA K VQWKVDNA ...String: MGWSCIILFL VATATGVHSE IVLTQSPATL SLSPGERATL SCRASQSVSS YLAWYQQKPG QAPRLLIYDA SNRATGIPAR FSGSGSGTD FTLTISSLEP EDFAVYYCQQ YEFFGQGTKL EIKRTVAAPS VFIFPPSDEQ LKSGTASVVC LLNNFYPREA K VQWKVDNA LQSGNSQESV TEQDSKDSTY SLSSTLTLSK ADYEKHKVYA CEVTHQGLSS PVTKSFNRGE C |
-Macromolecule #3: VRC01GL heavy chain
Macromolecule | Name: VRC01GL heavy chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 25.334305 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: (PCA)VQLVQSGAE VKKPGASVKV SCKASGYTFT GYYMHWVRQA PGQGLEWMGW INPNSGGTNY CQKFQGRVTM TRDTSI STA YMELSRLRSD DTAVYYCARG KNSDYNWDFQ HWGQGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPE PV TVSWNSGALT ...String: (PCA)VQLVQSGAE VKKPGASVKV SCKASGYTFT GYYMHWVRQA PGQGLEWMGW INPNSGGTNY CQKFQGRVTM TRDTSI STA YMELSRLRSD DTAVYYCARG KNSDYNWDFQ HWGQGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPE PV TVSWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKR VEPKSCDKTH HHHHH |
-Macromolecule #11: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 11 / Number of copies: 12 / Formula: NAG |
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Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7 |
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Grid | Model: C-flat-1.2/1.3 4C / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: COUNTING / Average electron dose: 1.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
CTF correction | Software - Name: Gctf |
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Final reconstruction | Applied symmetry - Point group: C3 (3 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.8 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Details: Frequency-limited refinement / Number images used: 134443 |
Initial angle assignment | Type: PROJECTION MATCHING / Software - Name: RELION |
Final angle assignment | Type: PROJECTION MATCHING / Software - Name: RELION |
-Atomic model buiding 1
Refinement | Protocol: OTHER |
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Output model | PDB-6myy: |