FC0032
Ciboulot  -  Actin

Biological function
Ciboulot or its isolated first βT domain (CibD1) make a complex with G-actin which, in contrast to sequestering β-Thymosins, participates in barbed end assembly like profilin:G-actin complex. This profilin-like activity accounts for Ciboulot in vivo function in axonal during metamorphosis.

Domain organization/sequence features
The WH2 domain is present in over 50 modular proteins, in which it might function in association with another domain of the protein to promote actin polymerization. The WH2 domain can also exist in tandem repeats of up to four WH2 motifs, separated by linkers of variable lengths. The length and/or sequence of the linkers have a non- trivial role in enabling each WH2 domain to bind actin, and in the spatial organization and dynamics of the complexes. Despite sequence differences, WH2 domains bind actin identically and possess versatile functions in actin assembly.

Structural evidence
Whether the WH2 domain inhibits or promotes actin assembly is largely determined by the dynamic interaction of the central and C-terminal regions of the WH2 domain with actin subdomains 1 and 2.

Biochemical evidence
Ciboulot can interact with G-actin in non-polymerizing low ionic strength conditions (G- buffer), more dynamically than thymosin β. These data suggested that the switch of function of βT domains from inhibition to promotion of actin assembly might depend on different still ill-defined interactions of their C-terminal region with actin subdomains 2 and 4, mediated by sequence variations widely distributed within their C-terminal half. Dynamics of Ciboulot could be decreased by introducing the Thymosine linker and increase the affinity for G-actin.

Mechanism category
competitive binding

Significance
Because actin subdomain-2 is itself disordered, the plasticity of WH2 might induce different structures of subdomain-2 upon binding.

Submitted by
Marie-France Carlier   marie-france.carlier@i2bc.paris-saclay.f