SASDDG2: Glycosylated Human Immunoglobulin G Fc Region (Glycosylated human...

Basic information

• Entry: Database: SASBDB / ID: SASDDG2

Sample

Glycosylated Human Immunoglobulin G Fc Region

• Glycosylated human immunoglobulin G Fc region (protein), gFc, 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: MAbs / Year: 2019; Title: C2 domain orientation of human immunoglobulin G in solution: Structural comparison of glycosylated and aglycosylated Fc regions using small-angle X-ray scattering.; Authors: Seiki Yageta / Hiroshi Imamura / Risa Shibuya / Shinya Honda / ; Abstract: The N-linked glycan in immunoglobulin G is critical for the stability and function of the crystallizable fragment (Fc) region. Alteration of these protein properties upon the removal of the N-linked glycan has often been explained by the alteration of the C2 domain orientation in the Fc region. To confirm this hypothesis, we examined the small-angle X-ray scattering (SAXS) profile of the glycosylated Fc region (gFc) and aglycosylated Fc region (aFc) in solution. Conformational characteristics of the C2 domain orientation were validated by comparison with SAXS profiles theoretically calculated from multiple crystal structures of the Fc region with different C2 domain orientations. The reduced chi-square values from the fitting analyses of gFc and aFc associated with the degree of openness or closure of each crystal structure, as determined from the first principal component that partially governed the variation of the C2 domain orientation extracted by a singular value decomposition analysis. For both gFc and aFc, the best-fitted SAXS profiles corresponded to ones calculated based on the crystal structure of gFc that formed a "semi-closed" C2 domain orientation. Collectively, the data indicated that the removal of the N-linked glycan only negligibly affected the C2 domain orientation in solution. These findings will guide the development of methodology for the production of highly refined functional Fc variants.

Contact author

• Seiki Yageta (AIST, National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan)

Models

• Model #2711: ; Type: atomic / Chi-square value: 0.020 / P-value: 0.020315; Search similar-shape structures of this assembly by Omokage search (details)

Sample

• Sample: Name: Glycosylated Human Immunoglobulin G Fc Region / Specimen concentration: 3.25 mg/ml
• Buffer: Name: 20 mM Citrate-Phosphate / pH: 7

Entity #920

Name: gFc / Type: protein / Description: Glycosylated human immunoglobulin G Fc region / Formula weight: 24.938 / 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 PG

Experimental information

• Beam: Instrument name: Photon Factory (PF), High Energy Accelerator Research Organization (KEK) BL-10C; City: Tsukuba / 国: Japan / Type of source: X-ray synchrotronSynchrotron / Wavelength: 0.12 Å / Dist. spec. to detc.: 2 mm
• Detector: Name: Pilatus3 2M / Pixsize x: 0.172 mm

Scan

Title: Glycosylated Human Immunoglobulin G Fc Region / Measurement date: Mar 5, 2017 / Cell temperature: 25 °C / Exposure time: 2 sec. / Number of frames: 15 / Unit: 1/A /

	Min	Max
Q	0.0101	0.3497

Distance distribution function P(R)

Sofotware P(R): GNOM 5.0 / Number of points: 331 /

	Min	Max
Q	0.019196	0.296245
P(R) point	1	331
R	0	102.1

Result

Type of curve: single_conc /

	Experimental	Standard	Porod
MW	53.7 kDa	53.7 kDa	-
Volume	-	-	66 nm3

	P(R)	Guinier	Guinier error
Forward scattering, I0	2052	0.039	-
Radius of gyration, Rg	2.79 nm	2.744 nm	0.15

	Min	Max
D	-	10.21
Guinier point	43	187