Formins regulate actin filament flexibility through long range allosteric interactions.
The members of the formin family nucleate actin polymerization and play essential roles in the regulation of the actin cytoskeleton during a wide range of cellular and developmental processes. In the present work, we describe the effects of mDia1-FH2 on the conformation of actin filaments by using a temperature-dependent fluorescence resonance energy transfer method. Our results revealed that actin filaments were more flexible in the presence than in the absence of formin. The effect strongly depends on the mDia1-FH2 concentration in a way that indicates that more than one mechanism is responsible for the formin effect. In accordance with the more flexible filament structure, the thermal stability of actin decreased and the rate of phosphate dissociation from actin filaments increased in the presence of formin. The interpretation of the results supports a model in which formin binding to barbed ends makes filaments more flexible through long range allosteric interactions, whereas binding of formin to the sides of the filaments stabilizes the protomer-protomer interactions. These results suggest that formins can regulate the conformation of actin filaments and may thus also modulate the affinity of actin-binding proteins to filaments nucleated/capped by formins.
Department of Biophysics, Faculty of Medicine, University of Pécs, Pécs, Szigeti str. 12, H-7624, Hungary.
Beáta
B
Bugyi
Gábor
G
Papp
Gábor
G
Hild
Dénes
D
Lõrinczy
Elisa M
EM
Nevalainen
Pekka
P
Lappalainen
Béla
B
Somogyi
Miklós
M
Nyitrai
D008841:Actin Cytoskeleton / Q000737:chemistry*; D000199:Actins / Q000737:chemistry; D000495:Allosteric Site; D000818:Animals; D002152:Calorimetry, Differential Scanning; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D019281:Dimerization; D005326:Fetal Proteins / Q000737:chemistry / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D000080865:Formins; D006358:Hot Temperature; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008956:Models, Chemical; D008968:Molecular Conformation; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010710:Phosphates / Q000737:chemistry; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry; D011506:Proteins / Q000737:chemistry; D013696:Temperature; D013816:Thermodynamics
D000199:Actins; D002352:Carrier Proteins; C491464:Diap1 protein, mouse; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009687:Nuclear Proteins; D010710:Phosphates; D021122:Protein Subunits; D011506:Proteins