1yy8
From Proteopedia
(New page: 200px<br /> <applet load="1yy8" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yy8, resolution 2.00Å" /> '''Crystal structure o...) |
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| - | [[Image:1yy8.gif|left|200px]]<br /> | + | [[Image:1yy8.gif|left|200px]]<br /><applet load="1yy8" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1yy8" size=" | + | |
caption="1yy8, resolution 2.00Å" /> | caption="1yy8, resolution 2.00Å" /> | ||
'''Crystal structure of the Fab fragment from the monoclonal antibody cetuximab/Erbitux/IMC-C225'''<br /> | '''Crystal structure of the Fab fragment from the monoclonal antibody cetuximab/Erbitux/IMC-C225'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Recent structural studies of epidermal growth factor receptor (EGFR) | + | Recent structural studies of epidermal growth factor receptor (EGFR) family extracellular regions have identified an unexpected mechanism for ligand-induced receptor dimerization that has important implications for activation and inhibition of these receptors. Here we describe the 2.8 angstroms resolution X-ray crystal structure of the antigen binding (Fab) fragment from cetuximab (Erbitux), an inhibitory anti-EGFR antibody, in complex with the soluble extracellular region of EGFR (sEGFR). The sEGFR is in the characteristic "autoinhibited" or "tethered" inactive configuration. Cetuximab interacts exclusively with domain III of sEGFR, partially occluding the ligand binding region on this domain and sterically preventing the receptor from adopting the extended conformation required for dimerization. We suggest that both these effects contribute to potent inhibition of EGFR activation. |
==About this Structure== | ==About this Structure== | ||
| - | 1YY8 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus/homo_sapiens Mus musculus/homo sapiens]. Full crystallographic information is available from [http:// | + | 1YY8 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Mus_musculus/homo_sapiens Mus musculus/homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YY8 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Mus musculus/homo sapiens]] | [[Category: Mus musculus/homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Ferguson, K | + | [[Category: Ferguson, K M.]] |
| - | [[Category: Jeffrey, P | + | [[Category: Jeffrey, P D.]] |
[[Category: Kussie, P.]] | [[Category: Kussie, P.]] | ||
[[Category: Li, S.]] | [[Category: Li, S.]] | ||
| - | [[Category: Schmitz, K | + | [[Category: Schmitz, K R.]] |
| - | [[Category: Wiltzius, J | + | [[Category: Wiltzius, J J.W.]] |
[[Category: fab fragment; antibody drug; cancer]] | [[Category: fab fragment; antibody drug; cancer]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:10:20 2008'' |
Revision as of 14:10, 21 February 2008
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Crystal structure of the Fab fragment from the monoclonal antibody cetuximab/Erbitux/IMC-C225
Overview
Recent structural studies of epidermal growth factor receptor (EGFR) family extracellular regions have identified an unexpected mechanism for ligand-induced receptor dimerization that has important implications for activation and inhibition of these receptors. Here we describe the 2.8 angstroms resolution X-ray crystal structure of the antigen binding (Fab) fragment from cetuximab (Erbitux), an inhibitory anti-EGFR antibody, in complex with the soluble extracellular region of EGFR (sEGFR). The sEGFR is in the characteristic "autoinhibited" or "tethered" inactive configuration. Cetuximab interacts exclusively with domain III of sEGFR, partially occluding the ligand binding region on this domain and sterically preventing the receptor from adopting the extended conformation required for dimerization. We suggest that both these effects contribute to potent inhibition of EGFR activation.
About this Structure
1YY8 is a Protein complex structure of sequences from Mus musculus/homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for inhibition of the epidermal growth factor receptor by cetuximab., Li S, Schmitz KR, Jeffrey PD, Wiltzius JJ, Kussie P, Ferguson KM, Cancer Cell. 2005 Apr;7(4):301-11. PMID:15837620
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