1y2o
From Proteopedia
(New page: 200px<br /> <applet load="1y2o" size="450" color="white" frame="true" align="right" spinBox="true" caption="1y2o, resolution 2.20Å" /> '''Structure of N-term...) |
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| - | [[Image:1y2o.gif|left|200px]]<br /> | + | [[Image:1y2o.gif|left|200px]]<br /><applet load="1y2o" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1y2o, resolution 2.20Å" /> | caption="1y2o, resolution 2.20Å" /> | ||
'''Structure of N-terminal domain IRSp53/BAIAP2'''<br /> | '''Structure of N-terminal domain IRSp53/BAIAP2'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The scaffolding protein insulin receptor tyrosine kinase substrate p53 | + | The scaffolding protein insulin receptor tyrosine kinase substrate p53 (IRSp53), a ubiquitous regulator of the actin cytoskeleton, mediates filopodia formation under the control of Rho-family GTPases. IRSp53 comprises a central SH3 domain, which binds to proline-rich regions of a wide range of actin regulators, and a conserved N-terminal IRSp53/MIM homology domain (IMD) that harbours F-actin-bundling activity. Here, we present the crystal structure of this novel actin-bundling domain revealing a coiled-coil domain that self-associates into a 180 A-long zeppelin-shaped dimer. Sedimentation velocity experiments confirm the presence of a single molecular species of twice the molecular weight of the monomer in solution. Mutagenesis of conserved basic residues at the extreme ends of the dimer abrogated actin bundling in vitro and filopodia formation in vivo, demonstrating that IMD-mediated actin bundling is required for IRSp53-induced filopodia formation. This study promotes an expanded view of IRSp53 as an actin regulator that integrates scaffolding and effector functions. |
==About this Structure== | ==About this Structure== | ||
| - | 1Y2O 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:// | + | 1Y2O 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=1Y2O OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bompard, G.]] | [[Category: Bompard, G.]] | ||
| - | [[Category: Dafforn, T | + | [[Category: Dafforn, T R.]] |
[[Category: Futterer, K.]] | [[Category: Futterer, K.]] | ||
| - | [[Category: Heung, M | + | [[Category: Heung, M Y.]] |
| - | [[Category: Machesky, L | + | [[Category: Machesky, L M.]] |
| - | [[Category: Millard, T | + | [[Category: Millard, T H.]] |
| - | [[Category: Scott, D | + | [[Category: Scott, D J.]] |
[[Category: actin bundling]] | [[Category: actin bundling]] | ||
[[Category: cell motility]] | [[Category: cell motility]] | ||
[[Category: filopodia]] | [[Category: filopodia]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:01:12 2008'' |
Revision as of 14:01, 21 February 2008
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Structure of N-terminal domain IRSp53/BAIAP2
Overview
The scaffolding protein insulin receptor tyrosine kinase substrate p53 (IRSp53), a ubiquitous regulator of the actin cytoskeleton, mediates filopodia formation under the control of Rho-family GTPases. IRSp53 comprises a central SH3 domain, which binds to proline-rich regions of a wide range of actin regulators, and a conserved N-terminal IRSp53/MIM homology domain (IMD) that harbours F-actin-bundling activity. Here, we present the crystal structure of this novel actin-bundling domain revealing a coiled-coil domain that self-associates into a 180 A-long zeppelin-shaped dimer. Sedimentation velocity experiments confirm the presence of a single molecular species of twice the molecular weight of the monomer in solution. Mutagenesis of conserved basic residues at the extreme ends of the dimer abrogated actin bundling in vitro and filopodia formation in vivo, demonstrating that IMD-mediated actin bundling is required for IRSp53-induced filopodia formation. This study promotes an expanded view of IRSp53 as an actin regulator that integrates scaffolding and effector functions.
About this Structure
1Y2O is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis of filopodia formation induced by the IRSp53/MIM homology domain of human IRSp53., Millard TH, Bompard G, Heung MY, Dafforn TR, Scott DJ, Machesky LM, Futterer K, EMBO J. 2005 Jan 26;24(2):240-50. Epub 2005 Jan 6. PMID:15635447
Page seeded by OCA on Thu Feb 21 16:01:12 2008
