The structure of FMNL2-Cdc42 yields insights into the mechanism of lamellipodia and filopodia formation.

2.50
Hdl Handle:
http://hdl.handle.net/10033/560406
Title:
The structure of FMNL2-Cdc42 yields insights into the mechanism of lamellipodia and filopodia formation.
Authors:
Kühn, Sonja; Erdmann, Constanze; Kage, Frieda; Block, Jennifer; Schwenkmezger, Lisa; Steffen, Anika; Rottner, Klemens; Geyer, Matthias
Abstract:
Formins 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.
Affiliation:
Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany.
Citation:
The structure of FMNL2-Cdc42 yields insights into the mechanism of lamellipodia and filopodia formation. 2015, 6:7088 Nat Commun
Journal:
Nature communications
Issue Date:
2015
URI:
http://hdl.handle.net/10033/560406
DOI:
10.1038/ncomms8088
PubMed ID:
25963737
Type:
Article
Language:
en
ISSN:
2041-1723
Appears in Collections:
publications of the Research group: molecular cell biology (MZBI)

Full metadata record

DC FieldValue Language
dc.contributor.authorKühn, Sonjaen
dc.contributor.authorErdmann, Constanzeen
dc.contributor.authorKage, Friedaen
dc.contributor.authorBlock, Jenniferen
dc.contributor.authorSchwenkmezger, Lisaen
dc.contributor.authorSteffen, Anikaen
dc.contributor.authorRottner, Klemensen
dc.contributor.authorGeyer, Matthiasen
dc.date.accessioned2015-07-14T14:34:49Zen
dc.date.available2015-07-14T14:34:49Zen
dc.date.issued2015en
dc.identifier.citationThe structure of FMNL2-Cdc42 yields insights into the mechanism of lamellipodia and filopodia formation. 2015, 6:7088 Nat Communen
dc.identifier.issn2041-1723en
dc.identifier.pmid25963737en
dc.identifier.doi10.1038/ncomms8088en
dc.identifier.urihttp://hdl.handle.net/10033/560406en
dc.description.abstractFormins 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.en
dc.language.isoenen
dc.titleThe structure of FMNL2-Cdc42 yields insights into the mechanism of lamellipodia and filopodia formation.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany.en
dc.identifier.journalNature communicationsen

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