1s78
From Proteopedia
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==Overview== | ==Overview== | ||
| - | We have determined the 3.2 A X-ray crystal structure of the extracellular | + | We have determined the 3.2 A X-ray crystal structure of the extracellular domain of the human epidermal growth factor receptor 2 (ErbB2 or HER2) in a complex with the antigen binding fragment of pertuzumab, an anti-ErbB2 monoclonal antibody also known as 2C4 or Omnitarg. Pertuzumab binds to ErbB2 near the center of domain II, sterically blocking a binding pocket necessary for receptor dimerization and signaling. The ErbB2-pertuzumab structure, combined with earlier mutagenesis data, defines the pertuzumab residues essential for ErbB2 interaction. To analyze the ErbB2 side of the interface, we have mutated a number of residues contacting pertuzumab and examined the effects of these mutations on pertuzumab binding and ErbB2-ErbB3 heterodimerization. We have also shown that conserved residues previously shown to be necessary for EGF receptor homodimerization may be dispensible for ErbB2-ErbB3 heterodimerization. |
==Disease== | ==Disease== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Transferase]] | [[Category: Transferase]] | ||
| - | [[Category: Carey, K | + | [[Category: Carey, K D.]] |
| - | [[Category: Franklin, M | + | [[Category: Franklin, M C.]] |
| - | [[Category: Leahy, D | + | [[Category: Leahy, D J.]] |
| - | [[Category: Sliwkowski, M | + | [[Category: Sliwkowski, M X.]] |
| - | [[Category: Vajdos, F | + | [[Category: Vajdos, F F.]] |
| - | [[Category: Vos, A | + | [[Category: Vos, A M.de.]] |
[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: cysteine-rich domain]] | [[Category: cysteine-rich domain]] | ||
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[[Category: receptor-antibody complex]] | [[Category: receptor-antibody complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:58:43 2008'' |
Revision as of 12:58, 21 February 2008
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Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex
Contents |
Overview
We have determined the 3.2 A X-ray crystal structure of the extracellular domain of the human epidermal growth factor receptor 2 (ErbB2 or HER2) in a complex with the antigen binding fragment of pertuzumab, an anti-ErbB2 monoclonal antibody also known as 2C4 or Omnitarg. Pertuzumab binds to ErbB2 near the center of domain II, sterically blocking a binding pocket necessary for receptor dimerization and signaling. The ErbB2-pertuzumab structure, combined with earlier mutagenesis data, defines the pertuzumab residues essential for ErbB2 interaction. To analyze the ErbB2 side of the interface, we have mutated a number of residues contacting pertuzumab and examined the effects of these mutations on pertuzumab binding and ErbB2-ErbB3 heterodimerization. We have also shown that conserved residues previously shown to be necessary for EGF receptor homodimerization may be dispensible for ErbB2-ErbB3 heterodimerization.
Disease
Known diseases associated with this structure: Adenocarcinoma of lung, somatic OMIM:[164870], Gastric cancer, somatic OMIM:[164870], Glioblastoma, somatic OMIM:[164870], Ovarian cancer, somatic, OMIM:[164870], Sialidosis, type I OMIM:[608272], Sialidosis, type II OMIM:[608272]
About this Structure
1S78 is a Single protein structure of sequence from Homo sapiens and Mus musculus with as ligand. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.
Reference
Insights into ErbB signaling from the structure of the ErbB2-pertuzumab complex., Franklin MC, Carey KD, Vajdos FF, Leahy DJ, de Vos AM, Sliwkowski MX, Cancer Cell. 2004 Apr;5(4):317-28. PMID:15093539
Page seeded by OCA on Thu Feb 21 14:58:43 2008
