1t44
From Proteopedia
(New page: 200px<br /> <applet load="1t44" size="450" color="white" frame="true" align="right" spinBox="true" caption="1t44, resolution 2.00Å" /> '''Structural basis of...) |
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| - | [[Image:1t44.gif|left|200px]]<br /> | + | [[Image:1t44.gif|left|200px]]<br /><applet load="1t44" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1t44" size=" | + | |
caption="1t44, resolution 2.00Å" /> | caption="1t44, resolution 2.00Å" /> | ||
'''Structural basis of actin sequestration by thymosin-B4: Implications for arp2/3 activation'''<br /> | '''Structural basis of actin sequestration by thymosin-B4: Implications for arp2/3 activation'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The WH2 (Wiscott-Aldridge syndrome protein homology domain 2) repeat is an | + | The WH2 (Wiscott-Aldridge syndrome protein homology domain 2) repeat is an actin interacting motif found in monomer sequestering and filament assembly proteins. We have stabilized the prototypical WH2 family member, thymosin-beta4 (Tbeta4), with respect to actin, by creating a hybrid between gelsolin domain 1 and the C-terminal half of Tbeta4 (G1-Tbeta4). This hybrid protein sequesters actin monomers, severs actin filaments and acts as a leaky barbed end cap. Here, we present the structure of the G1-Tbeta4:actin complex at 2 A resolution. The structure reveals that Tbeta4 sequesters by capping both ends of the actin monomer, and that exchange of actin between Tbeta4 and profilin is mediated by a minor overlap in binding sites. The structure implies that multiple WH2 motif-containing proteins will associate longitudinally with actin filaments. Finally, we discuss the role of the WH2 motif in arp2/3 activation. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1T44 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens,_mus_musculus Homo sapiens, mus musculus] and [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] with CA and ATP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1T44 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens,_mus_musculus Homo sapiens, mus musculus] and [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=ATP:'>ATP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T44 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Oryctolagus cuniculus]] | [[Category: Oryctolagus cuniculus]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
| - | [[Category: Aguda, A | + | [[Category: Aguda, A H.]] |
| - | [[Category: Burtnick, L | + | [[Category: Burtnick, L D.]] |
[[Category: Irobi, E.]] | [[Category: Irobi, E.]] | ||
[[Category: Larsson, M.]] | [[Category: Larsson, M.]] | ||
| - | [[Category: Robinson, R | + | [[Category: Robinson, R C.]] |
[[Category: ATP]] | [[Category: ATP]] | ||
[[Category: CA]] | [[Category: CA]] | ||
[[Category: structural protein]] | [[Category: structural protein]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:09:43 2008'' |
Revision as of 13:09, 21 February 2008
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Structural basis of actin sequestration by thymosin-B4: Implications for arp2/3 activation
Contents |
Overview
The WH2 (Wiscott-Aldridge syndrome protein homology domain 2) repeat is an actin interacting motif found in monomer sequestering and filament assembly proteins. We have stabilized the prototypical WH2 family member, thymosin-beta4 (Tbeta4), with respect to actin, by creating a hybrid between gelsolin domain 1 and the C-terminal half of Tbeta4 (G1-Tbeta4). This hybrid protein sequesters actin monomers, severs actin filaments and acts as a leaky barbed end cap. Here, we present the structure of the G1-Tbeta4:actin complex at 2 A resolution. The structure reveals that Tbeta4 sequesters by capping both ends of the actin monomer, and that exchange of actin between Tbeta4 and profilin is mediated by a minor overlap in binding sites. The structure implies that multiple WH2 motif-containing proteins will associate longitudinally with actin filaments. Finally, we discuss the role of the WH2 motif in arp2/3 activation.
Disease
Known diseases associated with this structure: Myopathy, actin, congenital, with cores OMIM:[102610], Myopathy, actin, congenital, with excess of thin myofilaments OMIM:[102610], Myopathy, congenital, with fiber-type disporportion 1 OMIM:[102610], Myopathy, nemaline, 3 OMIM:[102610]
About this Structure
1T44 is a Protein complex structure of sequences from Homo sapiens, mus musculus and Oryctolagus cuniculus with and as ligands. Full crystallographic information is available from OCA.
Reference
Structural basis of actin sequestration by thymosin-beta4: implications for WH2 proteins., Irobi E, Aguda AH, Larsson M, Guerin C, Yin HL, Burtnick LD, Blanchoin L, Robinson RC, EMBO J. 2004 Sep 15;23(18):3599-608. Epub 2004 Aug 26. PMID:15329672
Page seeded by OCA on Thu Feb 21 15:09:43 2008
