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1t44
From Proteopedia
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|PDB= 1t44 |SIZE=350|CAPTION= <scene name='initialview01'>1t44</scene>, resolution 2.00Å | |PDB= 1t44 |SIZE=350|CAPTION= <scene name='initialview01'>1t44</scene>, resolution 2.00Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=ATP:ADENOSINE-5'-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> |
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1p8z|1P8Z]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t44 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t44 OCA], [http://www.ebi.ac.uk/pdbsum/1t44 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1t44 RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=102610 102610]], Myopathy, actin, congenital, with excess of thin myofilaments OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=102610 102610]], Myopathy, congenital, with fiber-type disporportion 1 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=102610 102610]], Myopathy, nemaline, 3 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=102610 102610]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Larsson, M.]] | [[Category: Larsson, M.]] | ||
[[Category: Robinson, R C.]] | [[Category: Robinson, R C.]] | ||
| - | [[Category: ATP]] | ||
| - | [[Category: CA]] | ||
[[Category: structural protein]] | [[Category: structural protein]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 23 | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:51:01 2008'' |
Revision as of 20:51, 30 March 2008
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| , resolution 2.00Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Related: | 1P8Z
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Structural basis of actin sequestration by thymosin-B4: Implications for arp2/3 activation
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.
About this Structure
1T44 is a Protein complex structure of sequences from Homo sapiens, mus musculus and Oryctolagus cuniculus. 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 Sun Mar 30 23:51:01 2008
