4PL8

Structure of rabbit skeletal muscle actin in complex with a hybrid peptide comprising thymosin beta4 and the lysine-rich region of Cordon-Bleu

Summary for 4PL8

• Entry DOI: 10.2210/pdb4pl8/pdb
• Related: 4PL7
• Descriptor: Actin, alpha skeletal muscle, Thymosin beta-4,Protein cordon-bleu,Thymosin beta-4, ADENOSINE-5'-TRIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: contractile protein-structural protein complex, contractile protein/structural protein
• Biological source: Oryctolagus cuniculus (Rabbit); More
• Cellular location: Cytoplasm, cytoskeleton: P68135 P62328
• Total number of polymer chains: 3
• Total formula weight: 93179.18

Authors

Xue, B.,Robinson, R.C. (deposition date: 2014-05-16, release date: 2014-10-22, Last modification date: 2023-11-08)

Primary citation

Xue, B.,Leyrat, C.,Grimes, J.M.,Robinson, R.C.
Structural basis of thymosin-beta 4/profilin exchange leading to actin filament polymerization.
Proc.Natl.Acad.Sci.USA, 111:E4596-E4605, 2014

PubMed Abstract: Thymosin-β4 (Tβ4) and profilin are the two major sequestering proteins that maintain the pool of monomeric actin (G-actin) within cells of higher eukaryotes. Tβ4 prevents G-actin from joining a filament, whereas profilin:actin only supports barbed-end elongation. Here, we report two Tβ4:actin structures. The first structure shows that Tβ4 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 Tβ4 C-terminal helix interaction. These structures, combined with biochemical assays and molecular dynamics simulations, show that the exchange of bound actin between Tβ4 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.

PubMed: 25313062
DOI: 10.1073/pnas.1412271111

Experimental method

X-RAY DIFFRACTION (2 Å)