A novel mechanism of actin filament processive capping by formin: solution of the rotation paradox.
The FH2 domains of formin family proteins act as processive cappers of actin filaments. Previously suggested stair-stepping mechanisms of processive capping imply that a formin cap rotates persistently in one direction with respect to the filament. This challenges the formin-mediated mechanism of intracellular cable formation. We suggest a novel scenario of processive capping that is driven by developing and relaxing torsion elastic stresses. Based on the recently discovered crystal structure of an FH2-actin complex, we propose a second mode of processive capping-the screw mode. Within the screw mode, the formin dimer rotates with respect to the actin filament in the direction opposite to that generated by the stair-stepping mode so that a combination of the two modes prevents persistent torsion strain accumulation. We determine an optimal regime of processive capping, whose essence is a periodic switch between the stair-stepping and screw modes. In this regime, elastic energy does not exceed feasible values, and supercoiling of actin filaments is prevented.
Shemesh
Tom
T
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, 69978 Tel Aviv, Israel.
Otomo
Takanori
T
Rosen
Michael K
MK
Bershadsky
Alexander D
AD
Kozlov
Michael M
MM
D008841:Actin Cytoskeleton / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D019281:Dimerization; D004548:Elasticity; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D008954:Models, Biological; D009687:Nuclear Proteins; D017434:Protein Structure, Tertiary; D012399:Rotation
D000199:Actins; D005326:Fetal Proteins; D000080865:Formins; D008840:Microfilament Proteins; D009687:Nuclear Proteins