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5jih

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Revision as of 07:51, 10 June 2020

Crystal structure of HER2 binding IgG1-Fc (Fcab STAB19)

Structural highlights

5jih is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	5jik, 5jii
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.

Publication Abstract from PubMed

The crystallizable fragment (Fc) of the immunoglobulin class G (IgG) is an attractive scaffold for the design of novel therapeutics. Upon engineering the C-terminal loops in the CH3 domains, Fcabs (Fc domain with antigen-binding sites) can be designed. We present the first crystal structures of Fcabs, i.e., of the HER2-binding clone H10-03-6 having the AB and EF loop engineered and the stabilized version STAB19 derived by directed evolution. Comparison with the crystal structure of the Fc wild-type protein reveals conservation of the overall domain structures but significant differences in EF-loop conformations. Furthermore, we present the first Fcab-antigen complex structures demonstrating the interaction between the engineered Fcab loops with domain IV of HER2. The crystal structures of the STAB19-HER2 and H10-03-6-HER2 complexes together with analyses by isothermal titration calorimetry, SEC-MALS, and fluorescence correlation spectroscopy show that one homodimeric Fcab binds two HER2 molecules following a negative cooperative binding behavior.

Fcab-HER2 Interaction: a Menage a Trois. Lessons from X-Ray and Solution Studies.,Lobner E, Humm AS, Goritzer K, Mlynek G, Puchinger MG, Hasenhindl C, Ruker F, Traxlmayr MW, Djinovic-Carugo K, Obinger C Structure. 2017 Jun 6;25(6):878-889.e5. doi: 10.1016/j.str.2017.04.014. Epub 2017, May 18. PMID:28528777^[1]

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

References

↑ Lobner E, Humm AS, Goritzer K, Mlynek G, Puchinger MG, Hasenhindl C, Ruker F, Traxlmayr MW, Djinovic-Carugo K, Obinger C. Fcab-HER2 Interaction: a Menage a Trois. Lessons from X-Ray and Solution Studies. Structure. 2017 Jun 6;25(6):878-889.e5. doi: 10.1016/j.str.2017.04.014. Epub 2017, May 18. PMID:28528777 doi:http://dx.doi.org/10.1016/j.str.2017.04.014

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5jih"

@@ Line 1: / Line 1: @@
 ==Crystal structure of HER2 binding IgG1-Fc (Fcab STAB19)==
-<StructureSection load='5jih' size='340' side='right' caption='[[5jih]], [[Resolution|resolution]] 1.66&Aring;' scene=''>
+<StructureSection load='5jih' size='340' side='right'caption='[[5jih]], [[Resolution|resolution]] 1.66&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5jih]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JIH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JIH FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5jih]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JIH OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5JIH FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</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='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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5jik|5jik]], [[5jii|5jii]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5jih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jih OCA], [http://pdbe.org/5jih PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jih RCSB], [http://www.ebi.ac.uk/pdbsum/5jih PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jih ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5jih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jih OCA], [http://pdbe.org/5jih PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jih RCSB], [http://www.ebi.ac.uk/pdbsum/5jih PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jih ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 23: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
 [[Category: Djinovic-Carugo, K]]
 [[Category: Humm, A]]

5jih

From Proteopedia

Revision as of 07:51, 10 June 2020

Crystal structure of HER2 binding IgG1-Fc (Fcab STAB19)

Structural highlights

Disease

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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