Deville Célia, Girard-Blanc Christine, Assrir Nadine, Nhiri Naïma, Jacquet Eric, Bontems François, Renault Louis, Petres Stéphane, van Heijenoort Carine
Structural Chemistry and Biology Team, Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette, France.
Institut Pasteur, Paris, France.
FEBS Lett. 2016 Oct;590(20):3690-3699. doi: 10.1002/1873-3468.12423. Epub 2016 Oct 19.
Understanding the structural basis of actin cytoskeleton remodeling requires stabilization of actin monomers, oligomers, and filaments in complex with partner proteins, using various biochemical strategies. Here, we report a dramatic destabilization of the dynamic interaction with a model β-thymosin/WH2 domain induced by mutations in actin. This result underlines that mutant actins should be used with prudence to characterize interactions with intrinsically disordered partners as destabilization of dynamic interactions, although identifiable by NMR, may be invisible to other structural techniques. It also highlights how both β-thymosin/WH2 domains and actin tune local structure and dynamics in regulatory processes involving intrinsically disordered domains.
要理解肌动蛋白细胞骨架重塑的结构基础，需要运用各种生化策略，使肌动蛋白单体、寡聚体和细丝与伴侣蛋白形成复合物并实现稳定。在此，我们报告肌动蛋白中的突变会导致与模型β-胸腺素/WH2结构域的动态相互作用发生显著不稳定。这一结果强调，在利用突变型肌动蛋白来表征与内在无序伴侣的相互作用时应谨慎，因为动态相互作用的不稳定虽然可通过核磁共振识别，但可能对其他结构技术不可见。它还突出了β-胸腺素/WH2结构域和肌动蛋白在涉及内在无序结构域的调节过程中如何调节局部结构和动力学。
