4ydh | pdb_00004ydh
The structure of human FMNL1 N-terminal domains bound to Cdc42
Structural highlights
FunctionFMNL1_HUMAN May play a role in the control of cell motility and survival of macrophages (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the cortical actin filament dynamics and cell shape.[1] Publication Abstract from PubMedFormins are actin polymerization factors that elongate unbranched actin filaments at the barbed end. Rho family GTPases activate Diaphanous-related formins through the relief of an autoregulatory interaction. The crystal structures of the N-terminal domains of human FMNL1 and FMNL2 in complex with active Cdc42 show that Cdc42 mediates contacts with all five armadillo repeats of the formin with specific interactions formed by the Rho-GTPase insert helix. Mutation of three residues within Rac1 results in a gain-of-function mutation for FMNL2 binding and reconstitution of the Cdc42 phenotype in vivo. Dimerization of FMNL1 through a parallel coiled coil segment leads to formation of an umbrella-shaped structure that-together with Cdc42-spans more than 15 nm in diameter. The two interacting FMNL-Cdc42 heterodimers expose six membrane interaction motifs on a convex protein surface, the assembly of which may facilitate actin filament elongation at the leading edge of lamellipodia and filopodia. The structure of FMNL2-Cdc42 yields insights into the mechanism of lamellipodia and filopodia formation.,Kuhn S, Erdmann C, Kage F, Block J, Schwenkmezger L, Steffen A, Rottner K, Geyer M Nat Commun. 2015 May 12;6:7088. doi: 10.1038/ncomms8088. PMID:25963737[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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