title: FMNL3 FH2-actin structure gives insight into formin-mediated actin nucleation and elongation.
abstract: Formins are actin-assembly factors that act in a variety of actin-based processes. The conserved formin homology 2 (FH2) domain promotes filament nucleation and influences elongation through interaction with the barbed end. FMNL3 is a formin that induces assembly of filopodia but whose FH2 domain is a poor nucleator. The 3.4-Å structure of a mouse FMNL3 FH2 dimer in complex with tetramethylrhodamine-actin uncovers details of formin-regulated actin elongation. We observe distinct FH2 actin-binding regions; interactions in the knob and coiled-coil subdomains are necessary for actin binding, whereas those in the lasso-post interface are important for the stepping mechanism. Biochemical and cellular experiments test the importance of individual residues for function. This structure provides details for FH2-mediated filament elongation by processive capping and supports a model in which C-terminal non-FH2 residues of FMNL3 are required to stabilize the filament nucleus.
authors.affiliation: Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USA.
authors.forename: Morgan E
authors.initials: ME
authors.lastname: Thompson
authors.forename: Ernest G
authors.initials: EG
authors.lastname: Heimsath
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Gauvin
authors.forename: Henry N
authors.initials: HN
authors.lastname: Higgs
authors.forename: F Jon
authors.initials: FJ
authors.lastname: Kull
mesh_terms: D000199:Actins / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D018360:Crystallography, X-Ray; D000080865:Formins; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism / Q000648:ultrastructure; D012235:Rhodamines / Q000378:metabolism
chemical_list: D000199:Actins; C570808:FMNL3 protein, mouse; D000080865:Formins; D011506:Proteins; D012235:Rhodamines; C005358:tetramethylrhodamine