4b7i

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of Human IgG Fc Bearing Hybrid-type Glycans

Structural highlights

4b7i is a 2 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 2.36Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

IGHG1_HUMAN Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:254500. MM is a malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. Note=A chromosomal aberration involving IGHG1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus. Translocation t(11;14)(q13;q32) with CCND1; translocation t(4;14)(p16.3;q32.3) with FGFR3; translocation t(6;14)(p25;q32) with IRF4.

Function

IGHG1_HUMAN

Publication Abstract from PubMed

Human IgG Fc glycosylation modulates immunological effector functions such as antibody-dependent cellular cytotoxicity and phagocytosis. Engineering of Fc glycans therefore enables fine-tuning of the therapeutic properties of monoclonal antibodies. The N-linked glycans of Fc are typically complex-type, forming a network of noncovalent interactions along the protein surface of the Cgamma2 domain. Here, we manipulate the mammalian glycan-processing pathway to trap IgG1 Fc at sequential stages of maturation, from oligomannose- to hybrid- to complex-type glycans, and show that the Fc is structurally stabilized following the transition of glycans from their hybrid- to complex-type state. X-ray crystallographic analysis of this hybrid-type intermediate reveals that N-linked glycans undergo conformational changes upon maturation, including a flip within the trimannosyl core. Our crystal structure of this intermediate reveals a molecular basis for antibody biogenesis and provides a template for the structure-guided engineering of the protein-glycan interface of therapeutic antibodies.

Chemical and Structural Analysis of an Antibody Folding Intermediate Trapped during Glycan Biosynthesis.,Bowden TA, Baruah K, Coles CH, Harvey DJ, Yu X, Song BD, Stuart DI, Aricescu AR, Scanlan CN, Jones EY, Crispin M J Am Chem Soc. 2012 Oct 15. PMID:23025485^[1]

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

References

↑ Bowden TA, Baruah K, Coles CH, Harvey DJ, Yu X, Song BD, Stuart DI, Aricescu AR, Scanlan CN, Jones EY, Crispin M. Chemical and Structural Analysis of an Antibody Folding Intermediate Trapped during Glycan Biosynthesis. J Am Chem Soc. 2012 Oct 15. PMID:23025485 doi:http://dx.doi.org/10.1021/ja306068g

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4b7i"

@@ Line 3: / Line 3: @@
 <StructureSection load='4b7i' size='340' side='right'caption='[[4b7i]], [[Resolution|resolution]] 2.36&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4b7i]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B7I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B7I FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4b7i]] is a 2 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=4B7I OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4B7I 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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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]] 2.36&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1aj7|1aj7]], [[1aqk|1aqk]], [[1bey|1bey]], [[1d5b|1d5b]], [[1d5i|1d5i]], [[1d6v|1d6v]], [[1dn2|1dn2]], [[1e4k|1e4k]], [[1fc1|1fc1]], [[1fc2|1fc2]], [[1fcc|1fcc]], [[1h3t|1h3t]], [[1h3u|1h3u]], [[1h3v|1h3v]], [[1h3w|1h3w]], [[1h3y|1h3y]], [[1i7z|1i7z]], [[1l6x|1l6x]], [[1oqx|1oqx]], [[1t83|1t83]], [[1t89|1t89]], [[2iwg|2iwg]], [[2j6e|2j6e]], [[2rcs|2rcs]], [[2wah|2wah]], [[4acp|4acp]]</div></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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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=4b7i FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b7i OCA], [https://pdbe.org/4b7i PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4b7i RCSB], [https://www.ebi.ac.uk/pdbsum/4b7i PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4b7i ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[https://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN]] Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:[https://omim.org/entry/254500 254500]]. MM is a malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. Note=A chromosomal aberration involving IGHG1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus. Translocation t(11;14)(q13;q32) with CCND1; translocation t(4;14)(p16.3;q32.3) with FGFR3; translocation t(6;14)(p25;q32) with IRF4.
+[https://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN] Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:[https://omim.org/entry/254500 254500]. MM is a malignant tumor of plasma cells usually arising in the bone marrow and characterized by diffuse involvement of the skeletal system, hyperglobulinemia, Bence-Jones proteinuria and anemia. Complications of multiple myeloma are bone pain, hypercalcemia, renal failure and spinal cord compression. The aberrant antibodies that are produced lead to impaired humoral immunity and patients have a high prevalence of infection. Amyloidosis may develop in some patients. Multiple myeloma is part of a spectrum of diseases ranging from monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia. Note=A chromosomal aberration involving IGHG1 is found in multiple myeloma. Translocation t(11;14)(q13;q32) with the IgH locus. Translocation t(11;14)(q13;q32) with CCND1; translocation t(4;14)(p16.3;q32.3) with FGFR3; translocation t(6;14)(p25;q32) with IRF4.
+== Function ==
+[https://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN]
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Aricescu, A R]]
+[[Category: Aricescu AR]]
-[[Category: Baruah, K]]
+[[Category: Baruah K]]
-[[Category: Bowden, T A]]
+[[Category: Bowden TA]]
-[[Category: Coles, C H]]
+[[Category: Coles CH]]
-[[Category: Crispin, M]]
+[[Category: Crispin M]]
-[[Category: Harvey, D J]]
+[[Category: Harvey DJ]]
-[[Category: Jones, E Y]]
+[[Category: Jones EY]]
-[[Category: Scanlan, C N]]
+[[Category: Scanlan CN]]
-[[Category: Song, B D]]
+[[Category: Song BD]]
-[[Category: Stuart, D I]]
+[[Category: Stuart DI]]
-[[Category: Antibody]]
-[[Category: Hybrid]]
-[[Category: Igg]]
-[[Category: Immune system]]
-[[Category: Swainsonine]]

4b7i

From Proteopedia

Current revision

Crystal Structure of Human IgG Fc Bearing Hybrid-type Glycans

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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