Mutations in actin used for structural studies partially disrupt β-thymosin/WH2 domains interaction.
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.
Structural Chemistry and Biology Team, Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette, France.
Célia
C
Deville
Institut Pasteur, Paris, France.
Christine
C
Girard-Blanc
Structural Chemistry and Biology Team, Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette, France.
Nadine
N
Assrir
Structural Chemistry and Biology Team, Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette, France.
Naïma
N
Nhiri
Structural Chemistry and Biology Team, Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette, France.
Eric
E
Jacquet
Structural Chemistry and Biology Team, Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette, France.
François
F
Bontems
Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris Sud, Université Paris-Saclay, Gif-sur-Yvette, France.
Louis
L
Renault
Institut Pasteur, Paris, France.
Stéphane
S
Petres
Structural Chemistry and Biology Team, Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay, Gif-sur-Yvette, France. carine.van-heijenoort@cnrs.fr.
Carine
C
van Heijenoort
D000199:Actins / Q000737:chemistry / Q000235:genetics*; D000818:Animals; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D011817:Rabbits; D017386:Sequence Homology, Amino Acid; D013947:Thymosin / Q000737:chemistry*
D000199:Actins; D013947:Thymosin
NMR spectroscopy; actin; dynamic interaction; β-thymosin/WH2 domains