1T44

Structural basis of actin sequestration by thymosin-B4: Implications for arp2/3 activation

Summary for 1T44

• Entry DOI: 10.2210/pdb1t44/pdb
• Related: 1P8Z
• Descriptor: Chimera of Gelsolin domain 1 and C-Terminal domain of thymosin Beta-4, Actin, alpha, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: structural protein
• Biological source: Homo sapiens (human, house mouse); More
• Cellular location: Cytoplasm, cytoskeleton: P20065
• Total number of polymer chains: 2
• Total formula weight: 58533.06

Authors

Irobi, E.,Aguda, A.H.,Larsson, M.,Burtnick, L.D.,Robinson, R.C. (deposition date: 2004-04-28, release date: 2004-09-07, Last modification date: 2023-08-23)

Primary citation

Irobi, E.,Aguda, A.H.,Larsson, M.,Guerin, C.,Yin, H.L.,Burtnick, L.D.,Blanchoin, L.,Robinson, R.C.
Structural basis of actin sequestration by thymosin-beta4: implications for WH2 proteins.
Embo J., 23:3599-3608, 2004

PubMed Abstract: 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.

PubMed: 15329672
DOI: 10.1038/sj.emboj.7600372

Experimental method

X-RAY DIFFRACTION (2 Å)