Structural highlights
Publication Abstract from PubMed
Thymosin-beta4 (Tbeta4) and profilin are the two major sequestering proteins that maintain the pool of monomeric actin (G-actin) within cells of higher eukaryotes. Tbeta4 prevents G-actin from joining a filament, whereas profilin:actin only supports barbed-end elongation. Here, we report two Tbeta4:actin structures. The first structure shows that Tbeta4 has two helices that bind at the barbed and pointed faces of G-actin, preventing the incorporation of the bound G-actin into a filament. The second structure displays a more open nucleotide binding cleft on G-actin, which is typical of profilin:actin structures, with a concomitant disruption of the Tbeta4 C-terminal helix interaction. These structures, combined with biochemical assays and molecular dynamics simulations, show that the exchange of bound actin between Tbeta4 and profilin involves both steric and allosteric components. The sensitivity of profilin to the conformational state of actin indicates a similar allosteric mechanism for the dissociation of profilin during filament elongation.
Structural basis of thymosin-beta4/profilin exchange leading to actin filament polymerization.,Xue B, Leyrat C, Grimes JM, Robinson RC Proc Natl Acad Sci U S A. 2014 Oct 13. pii: 201412271. PMID:25313062[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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