National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
P41-GM10460
United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01 AI041239
United States
Citation
Journal: Elife / Year: 2020 Title: The structures of secretory and dimeric immunoglobulin A. Authors: Sonya Kumar Bharathkar / Benjamin W Parker / Andrey G Malyutin / Nandan Haloi / Kathryn E Huey-Tubman / Emad Tajkhorshid / Beth M Stadtmueller / Abstract: Secretory (S) Immunoglobulin (Ig) A is the predominant mucosal antibody, which binds pathogens and commensal microbes. SIgA is a polymeric antibody, typically containing two copies of IgA that ...Secretory (S) Immunoglobulin (Ig) A is the predominant mucosal antibody, which binds pathogens and commensal microbes. SIgA is a polymeric antibody, typically containing two copies of IgA that assemble with one joining-chain (JC) to form dimeric (d) IgA that is bound by the polymeric Ig-receptor ectodomain, called secretory component (SC). Here, we report the cryo-electron microscopy structures of murine SIgA and dIgA. Structures reveal two IgAs conjoined through four heavy-chain tailpieces and the JC that together form a β-sandwich-like fold. The two IgAs are bent and tilted with respect to each other, forming distinct concave and convex surfaces. In SIgA, SC is bound to one face, asymmetrically contacting both IgAs and JC. The bent and tilted arrangement of complex components limits the possible positions of both sets of antigen-binding fragments (Fabs) and preserves steric accessibility to receptor-binding sites, likely influencing antigen binding and effector functions.
History
Deposition
Jul 18, 2020
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Header (metadata) release
Nov 11, 2020
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Map release
Nov 11, 2020
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Update
Nov 11, 2020
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Current status
Nov 11, 2020
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Name: Igh protein / type: protein_or_peptide / ID: 1 Details: Genes encoding the mus musculus IgA HC constant region and the lambda LC constant region were fused with HC and LC variable region sequences to create complete HC and LC sequences. The HC ...Details: Genes encoding the mus musculus IgA HC constant region and the lambda LC constant region were fused with HC and LC variable region sequences to create complete HC and LC sequences. The HC and LC variable region is not modeled in this structure. Since authors have chosen not to provide complete sample sequence of the HC and LC variable region, the UNKs were not included in the sequence. Number of copies: 4 / Enantiomer: LEVO
Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 292 K / Instrument: FEI VITROBOT MARK IV Details: Wait time - 0s Drain time - 0s Blot time - 6s Blot Force - 5.
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Electron microscopy
Microscope
FEI TITAN KRIOS
Specialist optics
Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV
Image recording
Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Digitization - Dimensions - Width: 5760 pixel / Digitization - Dimensions - Height: 4092 pixel / Average electron dose: 60.0 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
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