Structural basis for the recruitment of profilin-actin complexes during filament elongation by Ena/VASP.
Cells sustain high rates of actin filament elongation by maintaining a large pool of actin monomers above the critical concentration for polymerization. Profilin-actin complexes constitute the largest fraction of polymerization-competent actin monomers. Filament elongation factors such as Ena/VASP and formin catalyze the transition of profilin-actin from the cellular pool onto the barbed end of growing filaments. The molecular bases of this process are poorly understood. Here we present structural and energetic evidence for two consecutive steps of the elongation mechanism: the recruitment of profilin-actin by the last poly-Pro segment of vasodilator-stimulated phosphoprotein (VASP) and the binding of profilin-actin simultaneously to this poly-Pro and to the G-actin-binding (GAB) domain of VASP. The actin monomer bound at the GAB domain is proposed to be in position to join the barbed end of the growing filament concurrently with the release of profilin.
Ferron
François
F
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Rebowski
Grzegorz
G
Lee
Sung Haeng
SH
Dominguez
Roberto
R
D008841:Actin Cytoskeleton / Q000737:chemistry; D000199:Actins / Q000737:chemistry*; D015815:Cell Adhesion Molecules / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003598:Cytoskeletal Proteins / Q000737:chemistry; D003599:Cytoskeleton / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry*; D008954:Models, Biological; D008968:Molecular Conformation; D010750:Phosphoproteins / Q000737:chemistry*; D051304:Profilins / Q000737:chemistry*; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D000098662:Vasodilator-Stimulated Phosphoprotein
D000199:Actins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D008840:Microfilament Proteins; D010750:Phosphoproteins; D051304:Profilins; D000098662:Vasodilator-Stimulated Phosphoprotein