+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-28278 | |||||||||
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Title | Hexameric IL-21 complex with IL-21R and IL-2Rg | |||||||||
Map data | sharpened map | |||||||||
Sample |
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Keywords | IL-21 / receptor / complex / signaling / CYTOKINE | |||||||||
Biological species | Homo sapiens (human) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.7 Å | |||||||||
Authors | Abhiraman GC / Jude KM / Caveney NA / Garcia KC | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Cell Rep / Year: 2023 Title: A structural blueprint for interleukin-21 signal modulation. Authors: Gita C Abhiraman / Theodora U J Bruun / Nathanael A Caveney / Leon L Su / Robert A Saxton / Qian Yin / Shaogeng Tang / Mark M Davis / Kevin M Jude / K Christopher Garcia / Abstract: Interleukin-21 (IL-21) plays a critical role in generating immunological memory by promoting the germinal center reaction, yet clinical use of IL-21 remains challenging because of its pleiotropy and ...Interleukin-21 (IL-21) plays a critical role in generating immunological memory by promoting the germinal center reaction, yet clinical use of IL-21 remains challenging because of its pleiotropy and association with autoimmune disease. To better understand the structural basis of IL-21 signaling, we determine the structure of the IL-21-IL-21R-γc ternary signaling complex by X-ray crystallography and a structure of a dimer of trimeric complexes using cryo-electron microscopy. Guided by the structure, we design analogs of IL-21 by introducing substitutions to the IL-21-γc interface. These IL-21 analogs act as partial agonists that modulate downstream activation of pS6, pSTAT3, and pSTAT1. These analogs exhibit differential activity on T and B cell subsets and modulate antibody production in human tonsil organoids. These results clarify the structural basis of IL-21 signaling and offer a potential strategy for tunable manipulation of humoral immunity. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_28278.map.gz | 56.6 MB | EMDB map data format | |
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Header (meta data) | emd-28278-v30.xml emd-28278.xml | 17.2 KB 17.2 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_28278_fsc.xml | 8.4 KB | Display | FSC data file |
Images | emd_28278.png | 88.4 KB | ||
Masks | emd_28278_msk_1.map | 64 MB | Mask map | |
Others | emd_28278_half_map_1.map.gz emd_28278_half_map_2.map.gz | 59.2 MB 59.2 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-28278 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-28278 | HTTPS FTP |
-Validation report
Summary document | emd_28278_validation.pdf.gz | 905.2 KB | Display | EMDB validaton report |
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Full document | emd_28278_full_validation.pdf.gz | 904.7 KB | Display | |
Data in XML | emd_28278_validation.xml.gz | 16.2 KB | Display | |
Data in CIF | emd_28278_validation.cif.gz | 20.9 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28278 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-28278 | HTTPS FTP |
-Related structure data
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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-Map
File | Download / File: emd_28278.map.gz / Format: CCP4 / Size: 64 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Annotation | sharpened map | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.151 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_28278_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: half map A
File | emd_28278_half_map_1.map | ||||||||||||
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Annotation | half map A | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map B
File | emd_28278_half_map_2.map | ||||||||||||
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Annotation | half map B | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : Hexameric IL-21 complex with IL-21R and IL-2Rg
Entire | Name: Hexameric IL-21 complex with IL-21R and IL-2Rg |
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Components |
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-Supramolecule #1: Hexameric IL-21 complex with IL-21R and IL-2Rg
Supramolecule | Name: Hexameric IL-21 complex with IL-21R and IL-2Rg / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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-Supramolecule #2: Interleukin-21
Supramolecule | Name: Interleukin-21 / type: complex / ID: 2 / Parent: 1 / Macromolecule list: #1 |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #3: Interleukin-21 receptor
Supramolecule | Name: Interleukin-21 receptor / type: complex / ID: 3 / Parent: 1 / Macromolecule list: #2 |
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Source (natural) | Organism: Homo sapiens (human) |
-Supramolecule #4: Cytokine receptor common subunit gamma
Supramolecule | Name: Cytokine receptor common subunit gamma / type: complex / ID: 4 / Parent: 1 / Macromolecule list: #3 |
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Source (natural) | Organism: Homo sapiens (human) |
-Macromolecule #1: Interleukin-21
Macromolecule | Name: Interleukin-21 / type: protein_or_peptide / ID: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: QGQDRHMIRM RQLIDIVDQL KNYVNDLVPE FLPAPEDVET NCEWSAFSCF QKAQLKSANT GNNERIIQVS IKKLKRKPPS TNAGRRQKHR LTCPSCDSYE KKPPKEFLER FKSLLQKMIH QHLSSRTHGS EDSGAPGSHH HHHH |
-Macromolecule #2: Interleukin-21 receptor
Macromolecule | Name: Interleukin-21 receptor / type: protein_or_peptide / ID: 2 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: CPDLVCYTDY LQTVICILEM WNLHPSTLTL TWQDQYEELK DEATSCSLHR SAHNATHATY TCHMDVFHFM ADDIFSVQIT DQSGQYSQEC GSFLLAESIK PAPPFDVTVT FSGQYQISWR SDYEDPAFYM LKGKLQYELQ YRNRGDPWAV SPRRKLISVD SRSVSLLPLE ...String: CPDLVCYTDY LQTVICILEM WNLHPSTLTL TWQDQYEELK DEATSCSLHR SAHNATHATY TCHMDVFHFM ADDIFSVQIT DQSGQYSQEC GSFLLAESIK PAPPFDVTVT FSGQYQISWR SDYEDPAFYM LKGKLQYELQ YRNRGDPWAV SPRRKLISVD SRSVSLLPLE FRKDSSYELQ VRAGPMPGSS YQGTWSEWSD PVIFQTQSEE KAASGRGLND IFEAQKIEWH EHHHHHH |
-Macromolecule #3: Cytokine receptor common subunit gamma
Macromolecule | Name: Cytokine receptor common subunit gamma / type: protein_or_peptide / ID: 3 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: PLPLPEVQCF VFNVEYMNCT WQSSSEPQPT NLTLHYWYKN SDNDKVQKCS HYLFSEEITS GCQLQKKEIH LYQTFVVQLQ DPREPRRQAT QMLKLQNLVI PWAPENLTLH KLSESQLELN WNNRFLNHCL EHLVQYRTDW DHSWTEQSVD YRHKFSLPSV DGQKRYTFRV ...String: PLPLPEVQCF VFNVEYMNCT WQSSSEPQPT NLTLHYWYKN SDNDKVQKCS HYLFSEEITS GCQLQKKEIH LYQTFVVQLQ DPREPRRQAT QMLKLQNLVI PWAPENLTLH KLSESQLELN WNNRFLNHCL EHLVQYRTDW DHSWTEQSVD YRHKFSLPSV DGQKRYTFRV RSRFNPLCGS AQHWSEWSHP IHWGSNTSKE NHHHHHH |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 3 mg/mL |
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Buffer | pH: 7.2 |
Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 200 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS GLACIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average exposure time: 5.0 sec. / Average electron dose: 49.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: OTHER / Nominal defocus max: 2.5 µm / Nominal defocus min: 1.0 µm |