8dir: Difference between revisions

Revision as of 10:10, 25 October 2023

The complex structure between human IgG1 Fc and its high affinity receptor FcgRI H174R variant

Structural highlights

8dir is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
Ligands:	BMA, FUC, GAL, MAN, NA, NAG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

FCGR1_HUMAN High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Understanding the molecular mechanism underlying the hierarchic binding between FcgammaRs and IgG antibodies is critical for therapeutic antibody engineering and FcgammaR functions. The recent determination of crystal structures of FcgammaRI-Fc complexes, however, resulted in two controversial mechanisms for the high affinity receptor binding to IgG. Here, we describe high resolution structures of a bovine FG-loop variant of FcgammaRI in complex with the Fc fragment of IgG(1) crystallized in three different conditions at neutral pH, confirming the characteristic FG loop-Fc interaction is critical to the high affinity immunoglobulin binding. We showed that the FcgammaRI D2-domain FG-loop functioned as a pH-sensing switch for IgG binding. Further live cell imaging of FcgammaRI-mediated internalization of immune complexes showed a pH sensitive temporal-spatial antibody-antigen uptake and release. Taken together, we demonstrate that the structures of FcgammaRI-Fc crystallized at neutral and acidic pH, respectively, represent the high and low affinity binding states of the receptor for IgG uptake and release. These results support a role for FcgammaRI in antigen delivery, highlight the importance of Fc glycan in antibody binding to the high affinity receptor and provide new insights to future antibody engineering.

FcgammaRI FG-loop functions as a pH sensitive switch for IgG binding and release.,Lu J, Spencer M, Zou Z, Traver M, Brzostowski J, Sun PD Front Immunol. 2023 Feb 6;14:1100499. doi: 10.3389/fimmu.2023.1100499. , eCollection 2023. PMID:36814926^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ van Vugt MJ, Heijnen AF, Capel PJ, Park SY, Ra C, Saito T, Verbeek JS, van de Winkel JG. FcR gamma-chain is essential for both surface expression and function of human Fc gamma RI (CD64) in vivo. Blood. 1996 May 1;87(9):3593-9. PMID:8611682
↑ Ernst LK, Duchemin AM, Miller KL, Anderson CL. Molecular characterization of six variant Fcgamma receptor class I (CD64) transcripts. Mol Immunol. 1998 Oct;35(14-15):943-54. PMID:9881690
↑ van Vugt MJ, Kleijmeer MJ, Keler T, Zeelenberg I, van Dijk MA, Leusen JH, Geuze HJ, van de Winkel JG. The FcgammaRIa (CD64) ligand binding chain triggers major histocompatibility complex class II antigen presentation independently of its associated FcR gamma-chain. Blood. 1999 Jul 15;94(2):808-17. PMID:10397749
↑ Edberg JC, Yee AM, Rakshit DS, Chang DJ, Gokhale JA, Indik ZK, Schreiber AD, Kimberly RP. The cytoplasmic domain of human FcgammaRIa alters the functional properties of the FcgammaRI.gamma-chain receptor complex. J Biol Chem. 1999 Oct 15;274(42):30328-33. PMID:10514529
↑ Lu J, Spencer M, Zou Z, Traver M, Brzostowski J, Sun PD. FcγRI FG-loop functions as a pH sensitive switch for IgG binding and release. Front Immunol. 2023 Feb 6;14:1100499. PMID:36814926 doi:10.3389/fimmu.2023.1100499

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] van Vugt MJ, Heijnen AF, Capel PJ, Park SY, Ra C, Saito T, Verbeek JS, van de Winkel JG. FcR gamma-chain is essential for both surface expression and function of human Fc gamma RI (CD64) in vivo. Blood. 1996 May 1;87(9):3593-9. PMID:8611682

[2] Ernst LK, Duchemin AM, Miller KL, Anderson CL. Molecular characterization of six variant Fcgamma receptor class I (CD64) transcripts. Mol Immunol. 1998 Oct;35(14-15):943-54. PMID:9881690

[3] van Vugt MJ, Kleijmeer MJ, Keler T, Zeelenberg I, van Dijk MA, Leusen JH, Geuze HJ, van de Winkel JG. The FcgammaRIa (CD64) ligand binding chain triggers major histocompatibility complex class II antigen presentation independently of its associated FcR gamma-chain. Blood. 1999 Jul 15;94(2):808-17. PMID:10397749

[4] Edberg JC, Yee AM, Rakshit DS, Chang DJ, Gokhale JA, Indik ZK, Schreiber AD, Kimberly RP. The cytoplasmic domain of human FcgammaRIa alters the functional properties of the FcgammaRI.gamma-chain receptor complex. J Biol Chem. 1999 Oct 15;274(42):30328-33. PMID:10514529

[5] Lu J, Spencer M, Zou Z, Traver M, Brzostowski J, Sun PD. FcγRI FG-loop functions as a pH sensitive switch for IgG binding and release. Front Immunol. 2023 Feb 6;14:1100499. PMID:36814926 doi:10.3389/fimmu.2023.1100499

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@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[8dir]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8DIR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DIR FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=GAL:BETA-D-GALACTOSE'>GAL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8dir FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dir OCA], [https://pdbe.org/8dir PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dir RCSB], [https://www.ebi.ac.uk/pdbsum/8dir PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dir ProSAT]</span></td></tr>
 </table>

8dir: Difference between revisions

Revision as of 10:10, 25 October 2023

The complex structure between human IgG1 Fc and its high affinity receptor FcgRI H174R variant

Structural highlights

Function

Publication Abstract from PubMed

References

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