Journal: Structure / Year: 2018 Title: Conformational Plasticity of the Immunoglobulin Fc Domain in Solution. Authors: Soumya G Remesh / Anthony A Armstrong / Andrew D Mahan / Jinquan Luo / Michal Hammel / Abstract: Fragment crystallizable (Fc) region of immunoglobulin G (IgG) antibody binds to specific Fc receptors (FcγRs) to control antibody effector functions. Currently, engineered specific Fc-FcγR ...Fragment crystallizable (Fc) region of immunoglobulin G (IgG) antibody binds to specific Fc receptors (FcγRs) to control antibody effector functions. Currently, engineered specific Fc-FcγR interactions are validated with a static conformation derived from the crystal structure. However, computational evidence suggests that the conformational variability of Fcs plays an important role in receptor recognition. Here we elucidate Fc flexibility of IgG1, IgG2, and IgG1 Fc with mutations (M255Y/S257T/T259E) in solution by small-angle X-ray scattering (SAXS). Measured SAXS profiles and experimental parameters show variations in flexibility between Fc isotypes. We develop and apply a modeling tool for an accurate conformational sampling of Fcs followed by SAXS fitting. Revealed conformational variability of the CH2 domain as low as 10 Å in displacement, illustrates the power of the atomistic modeling combined with SAXS. This inexpensive SAXS-based approach offers to improve the engineering of antibodies for tailoring Fc receptor interactions through altering and measuring Fc flexibility.
Contact author
Soumya G Remesh (Lawrence Berkeley National laboratory)
Instrument name: Advanced Light Source (ALS) 12.3.1 (SIBYLS) City: Berkeley, CA / 国: USA / Type of source: X-ray synchrotron / Wavelength: 0.103 Å / Dist. spec. to detc.: 1.5 mm
Detector
Name: Pilatus3 X 2M / Pixsize x: 172 mm
Scan
Title: Fc region of Immunoglobulin G2 (IgG2 Fc) / Measurement date: Feb 17, 2016 / Storage temperature: 4 °C / Cell temperature: 20 °C / Exposure time: 0.3 sec. / Number of frames: 33 / Unit: 1/A /
Min
Max
Q
0.0148
0.5397
Distance distribution function P(R)
Sofotware P(R): GNOM 5.0 / Number of points: 753 /
Min
Max
Q
0.01812
0.43777
P(R) point
1
753
R
0
90
Result
Type of curve: merged /
Experimental
Porod
MW
51 kDa
-
Volume
-
67 nm3
P(R)
P(R) error
Guinier
Guinier error
Forward scattering, I0
1.043
0.003
1.058
0.001
Radius of gyration, Rg
2.7 nm
0.003
2.77 nm
0.005
Min
Max
Error
D
-
9
0.01
Guinier point
3
60
-
+
About Yorodumi
-
News
-
Feb 9, 2022. New format data for meta-information of EMDB entries
New format data for meta-information of EMDB entries
Version 3 of the EMDB header file is now the official format.
The previous official version 1.9 will be removed from the archive.
In the structure databanks used in Yorodumi, some data are registered as the other names, "COVID-19 virus" and "2019-nCoV". Here are the details of the virus and the list of structure data.
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)
EMDB accession codes are about to change! (news from PDBe EMDB page)
The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
The EM Navigator/Yorodumi systems omit the EMD- prefix.
Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator
Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.
Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi