[English] 日本語

- EMDB-48575: G002-293-0536 Fab in complex with 001428_T278M_L14 SOSIP and RM20... -
+
Open data
-
Basic information
Entry | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Title | G002-293-0536 Fab in complex with 001428_T278M_L14 SOSIP and RM20A3 Fab | |||||||||
![]() | sharpened map | |||||||||
![]() |
| |||||||||
![]() | G002 / clinical trial / HIV-1 / VRC01 / human antibody / vaccine / Env / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex | |||||||||
Function / homology | ![]() positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane ...positive regulation of plasma membrane raft polarization / positive regulation of receptor clustering / host cell endosome membrane / clathrin-dependent endocytosis of virus by host cell / viral protein processing / fusion of virus membrane with host plasma membrane / fusion of virus membrane with host endosome membrane / viral envelope / virion attachment to host cell / host cell plasma membrane / virion membrane / structural molecule activity / membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
![]() | Phulera S / Ozorowski G / Ward AB | |||||||||
Funding support | ![]()
| |||||||||
![]() | ![]() Title: Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans. Authors: Jordan R Willis / Madhu Prabhakaran / Michelle Muthui / Ansuya Naidoo / Troy Sincomb / Weiwei Wu / Christopher A Cottrell / Elise Landais / Allan C deCamp / Nahid R Keshavarzi / Oleksandr ...Authors: Jordan R Willis / Madhu Prabhakaran / Michelle Muthui / Ansuya Naidoo / Troy Sincomb / Weiwei Wu / Christopher A Cottrell / Elise Landais / Allan C deCamp / Nahid R Keshavarzi / Oleksandr Kalyuzhniy / Jeong Hyun Lee / Linda M Murungi / Wilfrida A Ogonda / Nicole L Yates / Martin M Corcoran / Swastik Phulera / Joel Musando / Amanda Tsai / Gabrielle Lemire / Yiakon Sein / Michael Muteti / Praveen Alamuri / Jennifer A Bohl / Drienna Holman / Sunny Himansu / Brett Leav / Caroline Reuter / Li-An Lin / Baoyu Ding / Chunla He / Walter L Straus / Kellie J MacPhee / Isabel Regadas / Diana V Nyabundi / Ruth Chirchir / Aggrey Anzala / John N Kimotho / Caleb Kibet / Kelli Greene / Hongmei Gao / Erica Beatman / Kiara Benson / Dominick Laddy / David M Brown / Rhianna Bronson / Jalen Baptiste / Suprabhath Gajjala / Zahra Rikhtegaran-Tehrani / Alison Benner / Mukundhan Ramaswami / Danny Lu / Nushin Alavi / Sonya Amirzehni / Michael Kubitz / Ryan Tingle / Erik Georgeson / Nicole Phelps / Yumiko Adachi / Alessia Liguori / Claudia Flynn / Katherine McKenney / Xiaoya Zhou / D Collins Owuor / Sharon Owuor / Soo-Young Kim / Michael Duff / Ju Yeong Kim / Grace Gibson / Sabyasachi Baboo / Jolene Diedrich / Torben Schiffner / Marisa Shields / Mabela Matsoso / Jennifer Santos / Kristen Syvertsen / Allison Kennedy / Melissa Schroeter / Johan Vekemans / John Yates / James C Paulson / Ollivier Hyrien / Adrian B McDermott / Pholo Maenetje / Julien Nyombayire / Etienne Karita / Rosine Ingabire / Vinodh Edward / Vincent Muturi-Kioi / Janine Maenza / Adrienne E Shapiro / M Juliana McElrath / Srilatha Edupuganti / Barbara S Taylor / David Diemert / Gabriel Ozorowski / Richard A Koup / David Montefiori / Andrew B Ward / Gunilla Karlsson Hedestam / Georgia Tomaras / Devin J Hunt / Daniel Muema / Devin Sok / Dagna S Laufer / Sarah F Andrews / Eunice W Nduati / William R Schief / ![]() ![]() ![]() ![]() ![]() Abstract: A leading HIV vaccine strategy requires a priming immunogen to induce broadly neutralizing antibody (bnAb) precursors, followed by a series of heterologous boosters to elicit somatic hypermutation ...A leading HIV vaccine strategy requires a priming immunogen to induce broadly neutralizing antibody (bnAb) precursors, followed by a series of heterologous boosters to elicit somatic hypermutation (SHM) and produce bnAbs. In two randomized, open-label phase 1 human clinical trials, IAVI-G002 in the United States and IAVI-G003 in Rwanda and South Africa, we evaluated the safety and immunogenicity of mRNA-encoded nanoparticles as priming immunogens (both trials) and first-boosting immunogens (IAVI-G002). The vaccines were generally safe and well tolerated, except 18% of IAVI-G002 participants experienced skin reactions. Priming induced bnAb precursors with substantial frequencies and SHM, and heterologous boosting elicited increased SHM, affinity, and neutralization activity toward bnAb development. The results establish clinical proof of concept that heterologous boosting can advance bnAb-precursor maturation and demonstrate bnAb priming in Africa where the HIV burden is highest. | |||||||||
History |
|
-
Structure visualization
Supplemental images |
---|
-
Downloads & links
-EMDB archive
Map data | ![]() | 230.3 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 29.4 KB 29.4 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 13.3 KB | Display | ![]() |
Images | ![]() | 123 KB | ||
Masks | ![]() | 244.1 MB | ![]() | |
Filedesc metadata | ![]() | 8.9 KB | ||
Others | ![]() ![]() | 226.9 MB 226.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 1023.9 KB | Display | ![]() |
---|---|---|---|---|
Full document | ![]() | 1023.4 KB | Display | |
Data in XML | ![]() | 21.7 KB | Display | |
Data in CIF | ![]() | 28 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 9msdMC ![]() 9msyC M: atomic model generated by this map C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | sharpened map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.0052 Å | ||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Mask #1
File | ![]() | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: half map A
File | emd_48575_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half map A | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: half map B
File | emd_48575_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half map B | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : G002-293-0536 Fab in complex with 001428_T278M_L14 SOSIP and RM20...
Entire | Name: G002-293-0536 Fab in complex with 001428_T278M_L14 SOSIP and RM20A3 Fab |
---|---|
Components |
|
-Supramolecule #1: G002-293-0536 Fab in complex with 001428_T278M_L14 SOSIP and RM20...
Supramolecule | Name: G002-293-0536 Fab in complex with 001428_T278M_L14 SOSIP and RM20A3 Fab type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1, #5, #4, #2-#3 |
---|
-Macromolecule #1: 001428_T278M_L14 SOSIP gp140
Macromolecule | Name: 001428_T278M_L14 SOSIP gp140 / type: protein_or_peptide / ID: 1 Details: Envelope glycoprotein gp160 with 001428_T278M_L14 SOSIP gp140 engineered mutations Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 72.345602 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: ETGVENLWVT VYYGVPVWKE ARTTLFCASD AKAYETEVHN VWATHACVPT DPNPQEMVLG NVTENFNMWK NDMVDQMHED VISLWAQSL KPCVKLTPLC VTLECTQVNA TQGNTTQVNV TQVNGDEMKN CSFNTTTEIR DKKQKAYALF YRLDLVPLER E NRGDSNSA ...String: ETGVENLWVT VYYGVPVWKE ARTTLFCASD AKAYETEVHN VWATHACVPT DPNPQEMVLG NVTENFNMWK NDMVDQMHED VISLWAQSL KPCVKLTPLC VTLECTQVNA TQGNTTQVNV TQVNGDEMKN CSFNTTTEIR DKKQKAYALF YRLDLVPLER E NRGDSNSA SKYILINCNT SAITQACPKV NFDPIPIHYC TPAGYAILKC NNKTFNGTGS CNNVSTVQCT HGIKPVVSTQ LL LNGSLAE EEIIIRSENL MDNVKTIIVH LDQSVEIVCT RPNNNTVKSI RIGPGQTFYY TGDIIGNIRE AHCNISEKKW HEM LRRVSE KLAEHFPNKT IKFTSSSGGD LEITTHSFNC RGEFFYCNTS GLFNSTYMPN GTYMPNGTNN SNSTIILPCR IKQI INMWQ EVGRAMYAPP IAGNITCNSN ITGLLLVRDG GKNNNTEIFR PGGGDMRDNW RSELYKYKVV EIKPLGVAPT RCKRR VVGS HSGSGGSGSG GHAAVGLGAV SLGFLGAAGS TMGAASITLT VQARQLLSGI VQQQSNLLQA PEPQQHLLQD THWGIK QLQ TRVLAIEHYL KDQQLLGIWG CSGKLICCTA VPWNSSWSNK SLTDIWDNMT WMQWDREVSN YTGIIYRLLE DSQNQQE RN EQDLLALD UniProtKB: Envelope glycoprotein gp160 |
-Macromolecule #2: G002-293-0536 Fab heavy chain
Macromolecule | Name: G002-293-0536 Fab heavy chain / type: protein_or_peptide / ID: 2 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 24.206357 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: QVQLVQSGAE VKKPGASVKV SCKASGYSFT DYYIHWVRQA PGQGLEWMGW INPRFGGVNY AQKFQGRVTM TRDTSIRTAH MELSRLISD DTAFYYCARG RFADSVWNLL FWGQGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT ...String: QVQLVQSGAE VKKPGASVKV SCKASGYSFT DYYIHWVRQA PGQGLEWMGW INPRFGGVNY AQKFQGRVTM TRDTSIRTAH MELSRLISD DTAFYYCARG RFADSVWNLL FWGQGTLVTV SSASTKGPSV FPLAPSSKST SGGTAALGCL VKDYFPEPVT V SWNSGALT SGVHTFPAVL QSSGLYSLSS VVTVPSSSLG TQTYICNVNH KPSNTKVDKK VEPKSC |
-Macromolecule #3: G002-293-0536 Fab light chain
Macromolecule | Name: G002-293-0536 Fab light chain / type: protein_or_peptide / ID: 3 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 22.943395 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: DIQMTQSPSS LSASVGDRVT ITCQASQGIS NYLNWYQQKP GKAPKLLIYD ASNLETGVPS RFSGSGSGTD FTFTISGLQP EDIATYYCQ KYEFFGGGTK VEIKRTVAAP SVFIFPPSDE QLKSGTASVV CLLNNFYPRE AKVQWKVDNA LQSGNSQESV T EQDSKDST ...String: DIQMTQSPSS LSASVGDRVT ITCQASQGIS NYLNWYQQKP GKAPKLLIYD ASNLETGVPS RFSGSGSGTD FTFTISGLQP EDIATYYCQ KYEFFGGGTK VEIKRTVAAP SVFIFPPSDE QLKSGTASVV CLLNNFYPRE AKVQWKVDNA LQSGNSQESV T EQDSKDST YSLSSTLTLS KADYEKHKVY ACEVTHQGLS SPVTKSFNRG EC |
-Macromolecule #4: RM20A3 Fab light chain
Macromolecule | Name: RM20A3 Fab light chain / type: protein_or_peptide / ID: 4 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 22.82715 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: ALTQPPSVSG SPGQSVTISC TGTSSDIGSY NYVSWYQQHP GKAPKLMIYD VTQRPSGVSD RFSGSKSGNT ASLTISGLQA DDEADYYCS AYAGRQTFYI FGGGTRLTVL GQPKAAPSVT LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADSSPVK A GVETTTPS ...String: ALTQPPSVSG SPGQSVTISC TGTSSDIGSY NYVSWYQQHP GKAPKLMIYD VTQRPSGVSD RFSGSKSGNT ASLTISGLQA DDEADYYCS AYAGRQTFYI FGGGTRLTVL GQPKAAPSVT LFPPSSEELQ ANKATLVCLI SDFYPGAVTV AWKADSSPVK A GVETTTPS KQSNNKYAAS SYLSLTPEQW KSHRSYSCQV THEGSTVEKT VAPTECS |
-Macromolecule #5: RM20A3 Rab heavy chain
Macromolecule | Name: RM20A3 Rab heavy chain / type: protein_or_peptide / ID: 5 / Number of copies: 3 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 24.079055 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: EVQLVETGGG LVQPGGSLKL SCRASGYTFS SFAMSWVRQA PGKGLEWVSL INDRGGLTFY VDSVKGRFTI SRDNSKNTLS LQMHSLRDG DTAVYYCATG GMSSALQSSK YYFDFWGQGA LVTVSSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP E PVTVSWNS ...String: EVQLVETGGG LVQPGGSLKL SCRASGYTFS SFAMSWVRQA PGKGLEWVSL INDRGGLTFY VDSVKGRFTI SRDNSKNTLS LQMHSLRDG DTAVYYCATG GMSSALQSSK YYFDFWGQGA LVTVSSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP E PVTVSWNS GALTSGVHTF PAVLQSSGLY SLSSVVTVPS SSLGTQTYIC NVNHKPSNTK VDKKVEPKSC |
-Macromolecule #8: 2-acetamido-2-deoxy-beta-D-glucopyranose
Macromolecule | Name: 2-acetamido-2-deoxy-beta-D-glucopyranose / type: ligand / ID: 8 / Number of copies: 27 / Formula: NAG |
---|---|
Molecular weight | Theoretical: 221.208 Da |
Chemical component information | ![]() ChemComp-NAG: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Concentration | 8.2 mg/mL |
---|---|
Buffer | pH: 7.4 |
Grid | Model: UltrAuFoil R1.2/1.3 / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY / Pretreatment - Type: GLOW DISCHARGE |
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K / Instrument: FEI VITROBOT MARK IV |
-
Electron microscopy
Microscope | TFS GLACIOS |
---|---|
Image recording | Film or detector model: TFS FALCON 4i (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.7000000000000001 µm / Nominal magnification: 190000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |