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| | <StructureSection load='5f3b' size='340' side='right'caption='[[5f3b]], [[Resolution|resolution]] 1.76Å' scene=''> | | <StructureSection load='5f3b' size='340' side='right'caption='[[5f3b]], [[Resolution|resolution]] 1.76Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5f3b]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F3B OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5F3B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5f3b]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F3B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5F3B FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 1.76Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MSTN, GDF8 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=5f3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f3b OCA], [http://pdbe.org/5f3b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f3b RCSB], [http://www.ebi.ac.uk/pdbsum/5f3b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5f3b ProSAT]</span></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=5f3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f3b OCA], [https://pdbe.org/5f3b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5f3b RCSB], [https://www.ebi.ac.uk/pdbsum/5f3b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5f3b ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/GDF8_HUMAN GDF8_HUMAN]] Myostatin-related muscle hypertrophy. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/GDF8_HUMAN GDF8_HUMAN] Myostatin-related muscle hypertrophy. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GDF8_HUMAN GDF8_HUMAN]] Acts specifically as a negative regulator of skeletal muscle growth. | + | [https://www.uniprot.org/uniprot/GDF8_HUMAN GDF8_HUMAN] Acts specifically as a negative regulator of skeletal muscle growth. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | *[[Antibody 3D structures|Antibody 3D structures]] | | *[[Antibody 3D structures|Antibody 3D structures]] |
| | *[[Growth differentiation factor 3D STRUCTURES|Growth differentiation factor 3D STRUCTURES]] | | *[[Growth differentiation factor 3D STRUCTURES|Growth differentiation factor 3D STRUCTURES]] |
| | + | *[[3D structures of non-human antibody|3D structures of non-human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Mosyak, L]] | + | [[Category: Mosyak L]] |
| - | [[Category: Parris, K D]] | + | [[Category: Parris KD]] |
| - | [[Category: Antibody]]
| + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Myostatin]]
| + | |
| - | [[Category: Signaling protein-immune system complex]]
| + | |
| Structural highlights
Disease
GDF8_HUMAN Myostatin-related muscle hypertrophy. The disease is caused by mutations affecting the gene represented in this entry.
Function
GDF8_HUMAN Acts specifically as a negative regulator of skeletal muscle growth.
Publication Abstract from PubMed
Antibodies are an important class of biotherapeutics that offer specificity to their antigen, long half-life, effector function interaction and good manufacturability. The immunogenicity of non-human-derived antibodies, which can be a major limitation to development, has been partially overcome by humanization through complementarity-determining region (CDR) grafting onto human acceptor frameworks. The retention of foreign content in the CDR regions, however, is still a potential immunogenic liability. Here, we describe the humanization of an anti-myostatin antibody utilizing a 2-step process of traditional CDR-grafting onto a human acceptor framework, followed by a structure-guided approach to further reduce the murine content of CDR-grafted antibodies. To accomplish this, we solved the co-crystal structures of myostatin with the chimeric (Protein Databank (PDB) id 5F3B) and CDR-grafted anti-myostatin antibody (PDB id 5F3H), allowing us to computationally predict the structurally important CDR residues as well as those making significant contacts with the antigen. Structure-based rational design enabled further germlining of the CDR-grafted antibody, reducing the murine content of the antibody without affecting antigen binding. The overall "humanness" was increased for both the light and heavy chain variable regions.
Beyond CDR-grafting: Structure-guided humanization of framework and CDR regions of an anti-myostatin antibody.,Apgar JR, Mader M, Agostinelli R, Benard S, Bialek P, Johnson M, Gao Y, Krebs M, Owens J, Parris K, St Andre M, Svenson K, Morris C, Tchistiakova L MAbs. 2016 Oct;8(7):1302-1318. Epub 2016 Sep 13. PMID:27625211[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Apgar JR, Mader M, Agostinelli R, Benard S, Bialek P, Johnson M, Gao Y, Krebs M, Owens J, Parris K, St Andre M, Svenson K, Morris C, Tchistiakova L. Beyond CDR-grafting: Structure-guided humanization of framework and CDR regions of an anti-myostatin antibody. MAbs. 2016 Oct;8(7):1302-1318. Epub 2016 Sep 13. PMID:27625211 doi:http://dx.doi.org/10.1080/19420862.2016.1215786
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