1n8y
From Proteopedia
(New page: 200px<br /><applet load="1n8y" size="450" color="white" frame="true" align="right" spinBox="true" caption="1n8y, resolution 2.40Å" /> '''Crystal structure of...) |
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| - | [[Image:1n8y.jpg|left|200px]]<br /><applet load="1n8y" size=" | + | [[Image:1n8y.jpg|left|200px]]<br /><applet load="1n8y" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1n8y, resolution 2.40Å" /> | caption="1n8y, resolution 2.40Å" /> | ||
'''Crystal structure of the extracellular region of rat HER2'''<br /> | '''Crystal structure of the extracellular region of rat HER2'''<br /> | ||
==Overview== | ==Overview== | ||
| - | HER2 (also known as Neu, ErbB2) is a member of the epidermal growth factor | + | HER2 (also known as Neu, ErbB2) is a member of the epidermal growth factor receptor (EGFR; also known as ErbB) family of receptor tyrosine kinases, which in humans includes HER1 (EGFR, ERBB1), HER2, HER3 (ERBB3) and HER4 (ERBB4). ErbB receptors are essential mediators of cell proliferation and differentiation in the developing embryo and in adult tissues, and their inappropriate activation is associated with the development and severity of many cancers. Overexpression of HER2 is found in 20-30% of human breast cancers, and correlates with more aggressive tumours and a poorer prognosis. Anticancer therapies targeting ErbB receptors have shown promise, and a monoclonal antibody against HER2, Herceptin (also known as trastuzumab), is currently in use as a treatment for breast cancer. Here we report crystal structures of the entire extracellular regions of rat HER2 at 2.4 A and human HER2 complexed with the Herceptin antigen-binding fragment (Fab) at 2.5 A. These structures reveal a fixed conformation for HER2 that resembles a ligand-activated state, and show HER2 poised to interact with other ErbB receptors in the absence of direct ligand binding. Herceptin binds to the juxtamembrane region of HER2, identifying this site as a target for anticancer therapies. |
==About this Structure== | ==About this Structure== | ||
| - | 1N8Y is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with NAG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1N8Y is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] with <scene name='pdbligand=NAG:'>NAG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1N8Y OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Rattus norvegicus]] | [[Category: Rattus norvegicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Cho, H | + | [[Category: Cho, H S.]] |
| - | [[Category: Gabelli, S | + | [[Category: Gabelli, S B.]] |
| - | [[Category: Jr., D | + | [[Category: Jr., D W.Denney.]] |
| - | [[Category: Leahy, D | + | [[Category: Leahy, D J.]] |
[[Category: Mason, K.]] | [[Category: Mason, K.]] | ||
| - | [[Category: Ramyar, K | + | [[Category: Ramyar, K X.]] |
| - | [[Category: Stanley, A | + | [[Category: Stanley, A M.]] |
[[Category: NAG]] | [[Category: NAG]] | ||
[[Category: cell surface receptor]] | [[Category: cell surface receptor]] | ||
[[Category: tyrosin kinase receptor]] | [[Category: tyrosin kinase receptor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:03:31 2008'' |
Revision as of 12:03, 21 February 2008
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Crystal structure of the extracellular region of rat HER2
Overview
HER2 (also known as Neu, ErbB2) is a member of the epidermal growth factor receptor (EGFR; also known as ErbB) family of receptor tyrosine kinases, which in humans includes HER1 (EGFR, ERBB1), HER2, HER3 (ERBB3) and HER4 (ERBB4). ErbB receptors are essential mediators of cell proliferation and differentiation in the developing embryo and in adult tissues, and their inappropriate activation is associated with the development and severity of many cancers. Overexpression of HER2 is found in 20-30% of human breast cancers, and correlates with more aggressive tumours and a poorer prognosis. Anticancer therapies targeting ErbB receptors have shown promise, and a monoclonal antibody against HER2, Herceptin (also known as trastuzumab), is currently in use as a treatment for breast cancer. Here we report crystal structures of the entire extracellular regions of rat HER2 at 2.4 A and human HER2 complexed with the Herceptin antigen-binding fragment (Fab) at 2.5 A. These structures reveal a fixed conformation for HER2 that resembles a ligand-activated state, and show HER2 poised to interact with other ErbB receptors in the absence of direct ligand binding. Herceptin binds to the juxtamembrane region of HER2, identifying this site as a target for anticancer therapies.
About this Structure
1N8Y is a Single protein structure of sequence from Rattus norvegicus with as ligand. Full crystallographic information is available from OCA.
Reference
Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab., Cho HS, Mason K, Ramyar KX, Stanley AM, Gabelli SB, Denney DW Jr, Leahy DJ, Nature. 2003 Feb 13;421(6924):756-60. PMID:12610629
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