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- EMDB-25623: SIVmac239.K180S SOSIP in complex with FZ019.2 Fab -

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Basic information

Entry
Database: EMDB / ID: EMD-25623
TitleSIVmac239.K180S SOSIP in complex with FZ019.2 Fab
Map data
Sample
  • Complex: SIVmac239.K180S SOSIP trimer in complex with 1 copy of FZ019.2 Fab
    • Other: SIVmac239.K180S SOSIP
    • Other: FZ019.2 Fab Heavy Chain
    • Other: FZ019.2 Fab Light Chain
Biological speciesSimian immunodeficiency virus / Macaca mulatta (Rhesus monkey)
Methodsingle particle reconstruction / negative staining / Resolution: 23.0 Å
AuthorsBerndsen ZT
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)UM1 AI144462 United States
Bill & Melinda Gates FoundationOPP1196345/INV-008813 United States
CitationJournal: Nat Commun / Year: 2022
Title: Molecular insights into antibody-mediated protection against the prototypic simian immunodeficiency virus.
Authors: Fangzhu Zhao / Zachary T Berndsen / Nuria Pedreño-Lopez / Alison Burns / Joel D Allen / Shawn Barman / Wen-Hsin Lee / Srirupa Chakraborty / Sandrasegaram Gnanakaran / Leigh M Sewall / ...Authors: Fangzhu Zhao / Zachary T Berndsen / Nuria Pedreño-Lopez / Alison Burns / Joel D Allen / Shawn Barman / Wen-Hsin Lee / Srirupa Chakraborty / Sandrasegaram Gnanakaran / Leigh M Sewall / Gabriel Ozorowski / Oliver Limbo / Ge Song / Peter Yong / Sean Callaghan / Jessica Coppola / Kim L Weisgrau / Jeffrey D Lifson / Rebecca Nedellec / Thomas B Voigt / Fernanda Laurino / Johan Louw / Brandon C Rosen / Michael Ricciardi / Max Crispin / Ronald C Desrosiers / Eva G Rakasz / David I Watkins / Raiees Andrabi / Andrew B Ward / Dennis R Burton / Devin Sok /
Abstract: SIVmac239 infection of macaques is a favored model of human HIV infection. However, the SIVmac239 envelope (Env) trimer structure, glycan occupancy, and the targets and ability of neutralizing ...SIVmac239 infection of macaques is a favored model of human HIV infection. However, the SIVmac239 envelope (Env) trimer structure, glycan occupancy, and the targets and ability of neutralizing antibodies (nAbs) to protect against SIVmac239 remain unknown. Here, we report the isolation of SIVmac239 nAbs that recognize a glycan hole and the V1/V4 loop. A high-resolution structure of a SIVmac239 Env trimer-nAb complex shows many similarities to HIV and SIVcpz Envs, but with distinct V4 features and an extended V1 loop. Moreover, SIVmac239 Env has a higher glycan shield density than HIV Env that may contribute to poor or delayed nAb responses in SIVmac239-infected macaques. Passive transfer of a nAb protects macaques from repeated intravenous SIVmac239 challenge at serum titers comparable to those described for protection of humans against HIV infection. Our results provide structural insights for vaccine design and shed light on antibody-mediated protection in the SIV model.
History
DepositionDec 6, 2021-
Header (metadata) releaseOct 19, 2022-
Map releaseOct 19, 2022-
UpdateOct 19, 2022-
Current statusOct 19, 2022Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_25623.png

Downloads & links

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Map

FileDownload / File: emd_25623.map.gz / Format: CCP4 / Size: 2.8 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
4.02 Å/pix.
x 90 pix.
= 361.755 Å		4.02 Å/pix.
x 90 pix.
= 361.755 Å		4.02 Å/pix.
x 90 pix.
= 361.755 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 4.0195 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.0552
Minimum - Maximum-0.08326674 - 0.22374453
Average (Standard dev.)0.00073773175 (±0.011291879)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions909090
Spacing909090
CellA=B=C: 361.75497 Å
α=β=γ: 90.0 °

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Supplemental data

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Sample components

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Entire : SIVmac239.K180S SOSIP trimer in complex with 1 copy of FZ019.2 Fab

EntireName: SIVmac239.K180S SOSIP trimer in complex with 1 copy of FZ019.2 Fab
Components
  • Complex: SIVmac239.K180S SOSIP trimer in complex with 1 copy of FZ019.2 Fab
    • Other: SIVmac239.K180S SOSIP
    • Other: FZ019.2 Fab Heavy Chain
    • Other: FZ019.2 Fab Light Chain

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Supramolecule #1: SIVmac239.K180S SOSIP trimer in complex with 1 copy of FZ019.2 Fab

SupramoleculeName: SIVmac239.K180S SOSIP trimer in complex with 1 copy of FZ019.2 Fab
type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Simian immunodeficiency virus

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Macromolecule #1: SIVmac239.K180S SOSIP

MacromoleculeName: SIVmac239.K180S SOSIP / type: other / ID: 1 / Classification: other
Source (natural)Organism: Simian immunodeficiency virus
SequenceString: MGCLGNQLLI AILLLSVYGI YCTLYVTVFY GVPAWRNATI PLFCATKNRD TWGTTQCLPD NGDYSEMALN VTESFDAWNN TVTEQAIEDV WQLFETSIKP CVKLSPLCIT MRCNKSETDR WGLTKSITTT ASTTSTTASA KVDMVNETSS CIAQDNCTGL EQEQMISCKF ...String:
MGCLGNQLLI AILLLSVYGI YCTLYVTVFY GVPAWRNATI PLFCATKNRD TWGTTQCLPD NGDYSEMALN VTESFDAWNN TVTEQAIEDV WQLFETSIKP CVKLSPLCIT MRCNKSETDR WGLTKSITTT ASTTSTTASA KVDMVNETSS CIAQDNCTGL EQEQMISCKF NMTGLKRDKS KEYNETWYSA DLVCEQGNNT GNESRCYMNH CNTSVIQESC DKHYWDAIRF RYCAPPGYAL LRCNDTNYSG FMPKCSKVVV SSCTRMMETQ TSTWFGFNGT RAENRTYIYW HGRDNRTIIS LNKYYNLTMK CRRPGNKTVL PVTIMSGLVF HSQPINDRPK QAWCWFGGKW KDAIKEVKQT IVKHPRYTGT NNTDKINLTA PGGGDPEVTF MWTNCRGEFL YCKMNWFLNW VEDRNTANQK PKEQHKRNYV PCHIRQIINT WHKVGKNVYL PPREGDLTCN STVTSLIANI DWIDGNQTNI TMSAEVAELY RLELGDYKLV EITPIGLAPT SCKRYTTGGT SRRRRRRGVF VLGFLGFLAT AGSAMGAASL TLTAQSRTLL AGIVQQQQQL LDVPKRQQEL LRLTVWGTKN LQTRVTAIEK YLKDQAQLNA WGCAFRQVCC TTVPWPNASL IPKWNNETWQ EWERKVDFLE ENITALLEEA QIQQEKNMYE LQKLNGSGHH HHHHHH
Recombinant expressionOrganism: Homo sapiens (human)

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Macromolecule #2: FZ019.2 Fab Heavy Chain

MacromoleculeName: FZ019.2 Fab Heavy Chain / type: other / ID: 2 / Classification: other
Source (natural)Organism: Macaca mulatta (Rhesus monkey)
SequenceString: EVQLVESGPG LVKPSETLSL TCTVSGGSVT ANYYWNWIRQ PPGKGLEWIG NVYGNALVNY YNPSLKSRIT ISKDIFKDQF FLKLSSVTAA DTAVYYCARR GGNQYNYFDV WGPGVLVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV SWNSGALTSG ...String:
EVQLVESGPG LVKPSETLSL TCTVSGGSVT ANYYWNWIRQ PPGKGLEWIG NVYGNALVNY YNPSLKSRIT ISKDIFKDQF FLKLSSVTAA DTAVYYCARR GGNQYNYFDV WGPGVLVTVS SASTKGPSVF PLAPSSKSTS GGTAALGCLV KDYFPEPVTV SWNSGALTSG VHTFPAVLQS SGLYSLSSVV TVPSSSLGTQ TYICNVNHKP SNTKVDKKVE PKSC
Recombinant expressionOrganism: Homo sapiens (human)

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Macromolecule #3: FZ019.2 Fab Light Chain

MacromoleculeName: FZ019.2 Fab Light Chain / type: other / ID: 3 / Classification: other
Source (natural)Organism: Macaca mulatta (Rhesus monkey)
SequenceString: QAGLTQPASL SASPGASASL TCTFSGGINV TGYHIFWYQQ KPGSPPRFLL RYKSDSDKGQ GSGVPSRFSG SKHVSANTGI FRISGLQSED EADYYCAIDH SSGDVFGSGT KLTVLGQPKA APSVTLFPPS SEELQANKAT LVCLISDFYP GAVTVAWKAD SSPVKAGVET ...String:
QAGLTQPASL SASPGASASL TCTFSGGINV TGYHIFWYQQ KPGSPPRFLL RYKSDSDKGQ GSGVPSRFSG SKHVSANTGI FRISGLQSED EADYYCAIDH SSGDVFGSGT KLTVLGQPKA APSVTLFPPS SEELQANKAT LVCLISDFYP GAVTVAWKAD SSPVKAGVET TTPSKQSNNK YAASSYLSLT PEQWKSHKSY SCQVTHEGST VEKTVAPTEC S
Recombinant expressionOrganism: Homo sapiens (human)

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Experimental details

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Structure determination

Methodnegative staining
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration1 mg/mL
BufferpH: 7.4
StainingType: NEGATIVE / Material: uranyl formate

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Electron microscopy

MicroscopeFEI TECNAI SPIRIT
Image recordingFilm or detector model: FEI EAGLE (4k x 4k) / Detector mode: COUNTING / Average electron dose: 25.0 e/Å2
Electron beamAcceleration voltage: 120 kV / Electron source: LAB6
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.5 µm
Experimental equipment
Model: Tecnai Spirit / Image courtesy: FEI Company

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Image processing

CTF correctionSoftware - Name: Gctf
Final reconstructionResolution.type: BY AUTHOR / Resolution: 23.0 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: RELION / Number images used: 6060
Initial angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION
Final angle assignmentType: MAXIMUM LIKELIHOOD / Software - Name: RELION
FSC plot (resolution estimation)

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