1T44: Structural Basis Of Actin Sequestration By Thymosin-b4: Implications For 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.
PDB ID: 1T44Download
MMDB ID: 29409
PDB Deposition Date: 2004/4/28
Updated in MMDB: 2004/11
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Oryctolagus cuniculus
Similar Structures:
Biological Unit for 1T44: dimeric; determined by author and by software (PISA)
Molecular Components in 1T44
Label Count Molecule
Proteins (2 molecules)
Chimera of Gelsolin Domain 1 and C-terminal Domain of Thymosin Beta-4
Molecule annotation
Actin, Alpha
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB