5k33
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of extracellular domain of HER2 in complex with Fcab STAB19== | |
| + | <StructureSection load='5k33' size='340' side='right'caption='[[5k33]], [[Resolution|resolution]] 3.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5k33]] 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=5K33 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5K33 FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3Å</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=GOL:GLYCEROL'>GOL</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=5k33 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k33 OCA], [https://pdbe.org/5k33 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5k33 RCSB], [https://www.ebi.ac.uk/pdbsum/5k33 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5k33 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. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:28528777</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5k33" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Djinovic-Carugo K]] | ||
| + | [[Category: Goritzer K]] | ||
| + | [[Category: Humm A]] | ||
| + | [[Category: Lobner E]] | ||
| + | [[Category: Mlynek G]] | ||
| + | [[Category: Obinger C]] | ||
Current revision
Crystal structure of extracellular domain of HER2 in complex with Fcab STAB19
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