Cortactin Binding to F-actin Revealed by Electron Microscopy and 3D Reconstruction

Cortactin Adopts a Globular Conformation and Bundles Actin into Sheets

“…Lysine residues from the first and fourth actin-binding repeat and from the end of the helical region were cross-linked to a single lysine situated near the common protein-binding site of actin. This result is consistent with previous reports showing that the fourth actin-binding repeat of cortactin is involved in actin binding (37), as well as with the electron microscopy data that localize the actin-binding repeats close to the common protein-binding site of actin (20). This result demonstrates that the first and fourth repeats and the end of the helical domain are likely to be spatially close to each other, supporting the intramolecular cross-linking results.…”

“…In this model, the various cortactin domains act independently, and the protein functions passively by recruiting effector proteins to the correct location. The second structural study focused on a truncated construct of cortactin including only the f-actin-binding repeats domain and used cryo-electron microscopy to reveal an approximately spherical patch of density at the common protein-binding pocket of f-actin (20), a region on the surface of actin where most actin-binding proteins interact (21).…”

Cortactin in cell migration and cancer at a glance

“…Early sequence analysis and binding studies identified six central 'cortactin repeats' and demonstrated that the fourth repeat is required for direct binding to F-actin (Weed et al, 2000;Wu and Parsons, 1993). Structure prediction, circular dichroism and crosslinking studies suggest that the cortactin repeats are unstructured in solution and transition to a more stable conformation upon F-actin binding, which is in agreement with electron-microscopy models, but not necessarily with other molecular dynamics modeling (Pant et al, 2006;Shvetsov et al, 2009;Zhang et al, 2007). Regulation of F-actin binding might occur through alternative splicing within this region, as some splice variants show decreased affinity for F-actin (van Rossum et al, 2003).…”

Abl2/Abl-related Gene Stabilizes Actin Filaments, Stimulates Actin Branching by Actin-related Protein 2/3 Complex, and Promotes Actin Filament Severing by Cofilin

“…Low concentrations of cortactin inhibit actin filament severing by cofilin (Fig. 3B), likely by changing the filament conformation (30). Higher concentrations of cortactin have less effect on severing, perhaps by competing with cofilin for binding to the filament (Fig.…”