1toz
From Proteopedia
(New page: 200px<br /> <applet load="1toz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1toz" /> '''NMR structure of the human NOTCH-1 ligand b...) |
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'''NMR structure of the human NOTCH-1 ligand binding region'''<br /> | '''NMR structure of the human NOTCH-1 ligand binding region'''<br /> | ||
==Overview== | ==Overview== | ||
| - | We present NMR structural and dynamics analysis of the putative ligand | + | We present NMR structural and dynamics analysis of the putative ligand binding region of human Notch-1, comprising EGF-like domains 11-13. Functional integrity of an unglycosylated, recombinant fragment was confirmed by calcium-dependent binding of tetrameric complexes to ligand-expressing cells. EGF modules 11 and 12 adopt a well-defined, rod-like orientation rigidified by calcium. The interdomain tilt is similar to that found in previously studied calcium binding EGF pairs, but the angle of twist is significantly different. This leads to an extended double-stranded beta sheet structure, spanning the two EGF modules. Based on the conservation of residues involved in interdomain hydrophobic packing, we propose this arrangement to be prototypical of a distinct class of EGF linkages. On this premise, we have constructed a model of the 36 EGF modules of the Notch extracellular domain that enables predictions to be made about the general role of calcium binding to this region. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1TOZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1TOZ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TOZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Downing, A | + | [[Category: Downing, A K.]] |
[[Category: Hambleton, S.]] | [[Category: Hambleton, S.]] | ||
| - | [[Category: Handford, P | + | [[Category: Handford, P A.]] |
[[Category: Knott, V.]] | [[Category: Knott, V.]] | ||
| - | [[Category: Mcmichael, A | + | [[Category: Mcmichael, A J.]] |
[[Category: Muranyi, A.]] | [[Category: Muranyi, A.]] | ||
| - | [[Category: Valeyev, N | + | [[Category: Valeyev, N Y.]] |
| - | [[Category: Werner, J | + | [[Category: Werner, J M.]] |
[[Category: calcium binding]] | [[Category: calcium binding]] | ||
[[Category: egf]] | [[Category: egf]] | ||
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[[Category: notch]] | [[Category: notch]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:15:57 2008'' |
Revision as of 13:15, 21 February 2008
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NMR structure of the human NOTCH-1 ligand binding region
Contents |
Overview
We present NMR structural and dynamics analysis of the putative ligand binding region of human Notch-1, comprising EGF-like domains 11-13. Functional integrity of an unglycosylated, recombinant fragment was confirmed by calcium-dependent binding of tetrameric complexes to ligand-expressing cells. EGF modules 11 and 12 adopt a well-defined, rod-like orientation rigidified by calcium. The interdomain tilt is similar to that found in previously studied calcium binding EGF pairs, but the angle of twist is significantly different. This leads to an extended double-stranded beta sheet structure, spanning the two EGF modules. Based on the conservation of residues involved in interdomain hydrophobic packing, we propose this arrangement to be prototypical of a distinct class of EGF linkages. On this premise, we have constructed a model of the 36 EGF modules of the Notch extracellular domain that enables predictions to be made about the general role of calcium binding to this region.
Disease
Known diseases associated with this structure: Aortic valve disease OMIM:[190198], Leukemia, T-cell acute lymphoblastic OMIM:[190198]
About this Structure
1TOZ is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural and functional properties of the human notch-1 ligand binding region., Hambleton S, Valeyev NV, Muranyi A, Knott V, Werner JM, McMichael AJ, Handford PA, Downing AK, Structure. 2004 Dec;12(12):2173-83. PMID:15576031
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