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| | ==Structure of redesigned IgG1 first constant and lambda domains (CH1:Clambda constant redesign 1, CRD1) at 1.75A== | | ==Structure of redesigned IgG1 first constant and lambda domains (CH1:Clambda constant redesign 1, CRD1) at 1.75A== |
| - | <StructureSection load='4llm' size='340' side='right' caption='[[4llm]], [[Resolution|resolution]] 1.75Å' scene=''> | + | <StructureSection load='4llm' size='340' side='right'caption='[[4llm]], [[Resolution|resolution]] 1.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4llm]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LLM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LLM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4llm]] 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=4LLM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LLM FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lld|4lld]], [[4llq|4llq]], [[4llu|4llu]], [[4llw|4llw]], [[4lly|4lly]]</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]] 1.75Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IGHG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IGLC2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4llm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4llm OCA], [https://pdbe.org/4llm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4llm RCSB], [https://www.ebi.ac.uk/pdbsum/4llm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4llm ProSAT]</span></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=4llm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4llm OCA], [http://pdbe.org/4llm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4llm RCSB], [http://www.ebi.ac.uk/pdbsum/4llm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4llm ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/IGHG1_HUMAN IGHG1_HUMAN]] Defects in IGHG1 are a cause of multiple myeloma (MM) [MIM:[http://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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Atwell, S]] | + | [[Category: Large Structures]] |
| - | [[Category: Chamberlain, A K]] | + | [[Category: Atwell S]] |
| - | [[Category: Demarest, S J]] | + | [[Category: Chamberlain AK]] |
| - | [[Category: Guntas, G]] | + | [[Category: Demarest SJ]] |
| - | [[Category: Hansen-Estruch, C]] | + | [[Category: Guntas G]] |
| - | [[Category: Ho, C]] | + | [[Category: Hansen-Estruch C]] |
| - | [[Category: Huang, F]] | + | [[Category: Ho C]] |
| - | [[Category: Kuhlman, B]] | + | [[Category: Huang F]] |
| - | [[Category: Leaver-Fay, A]] | + | [[Category: Kuhlman B]] |
| - | [[Category: Lewis, S M]] | + | [[Category: Leaver-Fay A]] |
| - | [[Category: Pustilnik, A]] | + | [[Category: Lewis SM]] |
| - | [[Category: Sereno, A]] | + | [[Category: Pustilnik A]] |
| - | [[Category: Smith, E M]] | + | [[Category: Sereno A]] |
| - | [[Category: Truhlar, S M]] | + | [[Category: Smith EM]] |
| - | [[Category: Wu, X]] | + | [[Category: Truhlar SM]] |
| - | [[Category: Crd1]]
| + | [[Category: Wu X]] |
| - | [[Category: Igg domain]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Redesign]]
| + | |
| Structural highlights
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
Robust generation of IgG bispecific antibodies has been a long-standing challenge. Existing methods require extensive engineering of each individual antibody, discovery of common light chains, or complex and laborious biochemical processing. Here we combine computational and rational design approaches with experimental structural validation to generate antibody heavy and light chains with orthogonal Fab interfaces. Parental monoclonal antibodies incorporating these interfaces, when simultaneously co-expressed, assemble into bispecific IgG with improved heavy chain-light chain pairing. Bispecific IgGs generated with this approach exhibit pharmacokinetic and other desirable properties of native IgG, but bind target antigens monovalently. As such, these bispecific reagents may be useful in many biotechnological applications.
Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface.,Lewis SM, Wu X, Pustilnik A, Sereno A, Huang F, Rick HL, Guntas G, Leaver-Fay A, Smith EM, Ho C, Hansen-Estruch C, Chamberlain AK, Truhlar SM, Conner EM, Atwell S, Kuhlman B, Demarest SJ Nat Biotechnol. 2014 Feb;32(2):191-8. doi: 10.1038/nbt.2797. Epub 2014 Jan 26. PMID:24463572[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lewis SM, Wu X, Pustilnik A, Sereno A, Huang F, Rick HL, Guntas G, Leaver-Fay A, Smith EM, Ho C, Hansen-Estruch C, Chamberlain AK, Truhlar SM, Conner EM, Atwell S, Kuhlman B, Demarest SJ. Generation of bispecific IgG antibodies by structure-based design of an orthogonal Fab interface. Nat Biotechnol. 2014 Feb;32(2):191-8. doi: 10.1038/nbt.2797. Epub 2014 Jan 26. PMID:24463572 doi:http://dx.doi.org/10.1038/nbt.2797
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