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1: J Biol Chem. 2004 May 28;279(22):23637-45. Epub 2004 Mar 22.
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Coupling of folding and binding of thymosin beta4 upon interaction with monomeric actin monitored by nuclear magnetic resonance.

Domanski M, Hertzog M, Coutant J, Gutsche-Perelroizen I, Bontems F, Carlier MF, Guittet E, van Heijenoort C.

Institut de Chimie des Substances Naturelles, Laboratoire de Chimie et Biologie Structurales, CNRS, 1 Avenue de la Terrasse, F-91190 Gif sur Yvette, France.

Thymosin beta4 is a major actin-sequestering protein, yet the structural basis for its biological function is still unknown. This study provides insight regarding the way this 43-amino acid peptide, mostly unstructured in solution, binds to monomeric actin and prevents its assembly in filaments. We show here that the whole backbone of thymosin beta4 is highly affected upon binding to G-actin. The assignment of all amide protons and nitrogens of thymosin in the bound state, obtained using a combination of NMR experiments and selective labelings, shows that thymosin folds completely upon binding and displays a central extended region flanked by two N- and C-terminal helices. The cleavage of actin by subtilisin in the DNase I binding loop does not modify the structure of thymosin beta4 in the complex, showing that the backbone of the peptide is not in close proximity to segment 42-47 of actin. The combination of our NMR results and previously published mutation and cross-link data allows a better characterization of the binding mode of thymosins on G-actin.

PMID: 15039431 [PubMed - indexed for MEDLINE]