Disordered Motifs and Domains in Cell Control
Monday Speaker Abstracts
Control of Actin Filament Assembly by Multifunctional WASP- Homology 2 (WH2)
Domains
Marie-France Carlier
, Julien Perrnier, Pierre Montaville, Balendu Avvaru, Antoine Jégou,
Guillaume Romet-lemonne.
CNRS, Gif-sur-Yvette, France.
WH2 domains are widespread, intrinsically disordered, short (30 amino-acids) protein motifs
that fold upon binding to actin. They are present, in single or repeated motifs, in about 100
proteins that play a role in cell motility and morphogenetic processes by regulating actin
assembly. They all bind actin similarly, in particular inserting an amphipathic α-helix in a
hydrophobic pocket at the shear zone between actin subdomains 1 and 3 at the barbed face of the
actin monomer. Thus, they display a large variety of functions, from sequestration of monomeric
actin or profilin-mimicking activity to regulation of filament barbed end dynamics and filament
severing. We have analyzed the structural basis for the multifunctionality of several WH2
domain proteins like N-WASP, Spire, Cordon-bleu, VASP and the Vibrio cholerae effector
VopF. We show that 1) discrete sequence variations underlie differences in function ; 2) binding
of WH2 to barbed end terminal subunits allows barbed end capping by Spire, an essential feature
of its synergy with formin 2 in meiosis ; 3) a combination of profilin-like activity, filament
severing and ADP-G-actin sequestering generates enhanced filament dynamics and oscillatory
polymerization of actin ; 4) dimerization of WH2 domains allows filament barbed end tracking
and potential processive assembly in VASP and VopF.
References :
• Hertzog et al., 2004, Cell 117, 611-623.
• Bosch et al., 2007, Mol. Cell 28, 555-568.
• Husson et al., 2011, Cordon-Bleu uses WH2 domains as multifunctional dynamizers of actin
filament assembly. Mol. Cell 43, 464-477.
• Carlier 2011 Nat. Struct. Mol. Biol. 18, 967-969.
• Pernier et al., 2013, Nat. Struct. Mol. Biol. 20, 1069-1076.
• Montaville et al., 2014, PloS Biol. 12, e1001795.
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