1wyx
From Proteopedia
(New page: 200px<br /> <applet load="1wyx" size="450" color="white" frame="true" align="right" spinBox="true" caption="1wyx, resolution 1.14Å" /> '''The Crystal Structu...) |
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| - | [[Image:1wyx.gif|left|200px]]<br /> | + | [[Image:1wyx.gif|left|200px]]<br /><applet load="1wyx" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1wyx, resolution 1.14Å" /> | caption="1wyx, resolution 1.14Å" /> | ||
'''The Crystal Structure of the p130Cas SH3 Domain at 1.1 A Resolution'''<br /> | '''The Crystal Structure of the p130Cas SH3 Domain at 1.1 A Resolution'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The Crk-associated tyrosine kinase substrate p130cas (CAS) is a docking | + | The Crk-associated tyrosine kinase substrate p130cas (CAS) is a docking protein containing an SH3 domain near its N terminus, followed by a short proline-rich segment, a large central substrate domain composed of 15 repeats of the four amino acid sequence YxxP, a serine-rich region and a carboxy-terminal domain, which possesses consensus binding sites for the SH2 and SH3 domains of Src (YDYV and RPLPSPP, respectively). The SH3 domain of CAS mediates its interaction with several proteins involved in signaling pathways such as focal adhesion kinase (FAK), tyrosine phosphatases PTP1B and PTP-PEST, and the guanine nucleotide exchange factor C3G. As a homolog of the corresponding Src docking domain, the CAS SH3 domain binds to proline-rich sequences (PxxP) of its interacting partners that can adopt a polyproline type II helix. We have determined a high-resolution X-ray structure of the recombinant human CAS SH3 domain. The domain, residues 1-69, crystallized in two related space groups, P2(1) and C222(1), that provided diffraction data to 1.1 A and 2.1 A, respectively. The crystal structure shows, in addition to the conserved SH3 domain architecture, the way in which the CAS characteristic amino acids form an atypically charged ligand-binding surface. This arrangement provides a rationale for the unusual ligand recognition motif exhibited by the CAS SH3 domain. The structure enables modelling of the docking interactions to its ligands, for example from focal adhesion kinase, and supports structure-based drug design of inhibitors of the CAS-FAK interaction. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1WYX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG and EDO as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1WYX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=EDO:'>EDO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WYX OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Bossenmaier, B.]] | [[Category: Bossenmaier, B.]] | ||
[[Category: Dangl, M.]] | [[Category: Dangl, M.]] | ||
| - | [[Category: Engh, R | + | [[Category: Engh, R A.]] |
[[Category: Georges, G.]] | [[Category: Georges, G.]] | ||
[[Category: Hesse, F.]] | [[Category: Hesse, F.]] | ||
[[Category: Huber, R.]] | [[Category: Huber, R.]] | ||
[[Category: Ioannidis, I.]] | [[Category: Ioannidis, I.]] | ||
| - | [[Category: Kuenkele, K | + | [[Category: Kuenkele, K P.]] |
[[Category: Wisniewska, M.]] | [[Category: Wisniewska, M.]] | ||
[[Category: EDO]] | [[Category: EDO]] | ||
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[[Category: beta sheets]] | [[Category: beta sheets]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:49:32 2008'' |
Revision as of 13:49, 21 February 2008
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The Crystal Structure of the p130Cas SH3 Domain at 1.1 A Resolution
Contents |
Overview
The Crk-associated tyrosine kinase substrate p130cas (CAS) is a docking protein containing an SH3 domain near its N terminus, followed by a short proline-rich segment, a large central substrate domain composed of 15 repeats of the four amino acid sequence YxxP, a serine-rich region and a carboxy-terminal domain, which possesses consensus binding sites for the SH2 and SH3 domains of Src (YDYV and RPLPSPP, respectively). The SH3 domain of CAS mediates its interaction with several proteins involved in signaling pathways such as focal adhesion kinase (FAK), tyrosine phosphatases PTP1B and PTP-PEST, and the guanine nucleotide exchange factor C3G. As a homolog of the corresponding Src docking domain, the CAS SH3 domain binds to proline-rich sequences (PxxP) of its interacting partners that can adopt a polyproline type II helix. We have determined a high-resolution X-ray structure of the recombinant human CAS SH3 domain. The domain, residues 1-69, crystallized in two related space groups, P2(1) and C222(1), that provided diffraction data to 1.1 A and 2.1 A, respectively. The crystal structure shows, in addition to the conserved SH3 domain architecture, the way in which the CAS characteristic amino acids form an atypically charged ligand-binding surface. This arrangement provides a rationale for the unusual ligand recognition motif exhibited by the CAS SH3 domain. The structure enables modelling of the docking interactions to its ligands, for example from focal adhesion kinase, and supports structure-based drug design of inhibitors of the CAS-FAK interaction.
Disease
Known diseases associated with this structure: Albinism, brown OMIM:[115501], Albinism, rufous OMIM:[115501]
About this Structure
1WYX is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.
Reference
The 1.1 A resolution crystal structure of the p130cas SH3 domain and ramifications for ligand selectivity., Wisniewska M, Bossenmaier B, Georges G, Hesse F, Dangl M, Kunkele KP, Ioannidis I, Huber R, Engh RA, J Mol Biol. 2005 Apr 15;347(5):1005-14. PMID:15784259
Page seeded by OCA on Thu Feb 21 15:49:32 2008
Categories: Homo sapiens | Single protein | Bossenmaier, B. | Dangl, M. | Engh, R A. | Georges, G. | Hesse, F. | Huber, R. | Ioannidis, I. | Kuenkele, K P. | Wisniewska, M. | EDO | MG | Beta sheets
