SASDDT4: Fc region of Immunoglobulin G1 (IgG1 Fc) (Immunoglobulin heavy co...

Basic information

• Entry: Database: SASBDB / ID: SASDDT4

Sample

Fc region of Immunoglobulin G1 (IgG1 Fc)

• Immunoglobulin heavy constant gamma 1 (protein), IgG1 Fc, Homo sapiens

Function / homology

Function:

complement-dependent cytotoxicity / antibody-dependent cellular cytotoxicity / Fc-gamma receptor I complex binding / Classical antibody-mediated complement activation / Initial triggering of complement / immunoglobulin complex, circulating / IgG immunoglobulin complex / immunoglobulin receptor binding / FCGR activation / Role of phospholipids in phagocytosis / complement activation, classical pathway / antigen binding / FCGR3A-mediated IL10 synthesis / Regulation of Complement cascade / FCGR3A-mediated phagocytosis / B cell receptor signaling pathway / Regulation of actin dynamics for phagocytic cup formation / antibacterial humoral response / Interleukin-4 and Interleukin-13 signaling / blood microparticle / adaptive immune response / extracellular space / extracellular exosome / extracellular region / plasma membrane

Domain/homology:

Immunoglobulin/major histocompatibility complex, conserved site / Immunoglobulins and major histocompatibility complex proteins signature. / Immunoglobulin C-Type / Immunoglobulin C1-set / Immunoglobulin C1-set domain / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Immunoglobulin-like fold

Component:

Immunoglobulin heavy constant gamma 1

• Biological species: Homo sapiens (human)
• Citation: 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 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)

Models

• Model #1823: ; Type: atomic / Chi-square value: 0.641398787111; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Fc region of Immunoglobulin G1 (IgG1 Fc) / Specimen concentration: 1.00-14.00
• Buffer: Name: 20mM HEPES, 50mM NaCl / pH: 7.5

Entity #998

Name: IgG1 Fc / Type: protein / Description: Immunoglobulin heavy constant gamma 1 / Formula weight: 26.4 / Num. of mol.: 2 / Source: Homo sapiens / References: UniProt: P01857
Sequence:

TCPPCPAPEL LGGPSVFLFP PKPKDTLMIS RTPEVTCVVV DVSHEDPEVK FNWYVDGVEV HNAKTKPREE QYNSTYRVVS VLTVLHQDWL NGKEYKCKVS NKALPAPIEK TISKAKGQPR EPQVYTLPPS RDELTKNQVS LTCLVKGFYP SDIAVEWESN GQPENNYKTT PPVLDSDGSF FLYSKLTVDK SRWQQGNVFS CSVMHEALHN HYTQKSLSLS PGK

Experimental information

• Beam: Instrument name: Advanced Light Source (ALS) 12.3.1 (SIBYLS); City: Berkeley, CA / 国: USA / Type of source: X-ray synchrotronSynchrotron / 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 G1 (IgG1 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	0.012	0.5313

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 753 /

	Min	Max
Q	0.01533	0.43498
P(R) point	1	753
R	0	100

Result

Type of curve: merged /

	Experimental	Porod
MW	51 kDa	-
Volume	-	70 nm3

	P(R)	P(R) error	Guinier	Guinier error
Forward scattering, I0	420.1	0.7	414.42	1.07
Radius of gyration, Rg	2.7 nm	0.005	2.64 nm	0.009

	Min	Max
D	-	10
Guinier point	5	66