| First Author | Pant K | Year | 2006 |
| Journal | J Mol Biol | Volume | 359 |
| Issue | 4 | Pages | 840-7 |
| PubMed ID | 16697006 | Mgi Jnum | J:114869 |
| Mgi Id | MGI:3690276 | Doi | 10.1016/j.jmb.2006.03.065 |
| Citation | Pant K, et al. (2006) Cortactin binding to F-actin revealed by electron microscopy and 3D reconstruction. J Mol Biol 359(4):840-7 |
| abstractText | Cortactin and WASP activate Arp2/3-mediated actin filament nucleation and branching. However, different mechanisms underlie activation by the two proteins, which rely on distinct actin-binding modules and modes of binding to actin filaments. It is generally thought that cortactin binds to 'mother' actin filaments, while WASP donates actin monomers to Arp2/3-generated 'daughter' filament branches. Interestingly, cortactin also binds WASP in addition to F-actin and the Arp2/3 complex. However, the structural basis for the role of cortactin in filament branching remains unknown, making interpretation difficult. Here, electron microscopy and 3D reconstruction were carried out on F-actin decorated with the actin-binding repeating domain of cortactin, revealing conspicuous density on F-actin attributable to cortactin that is located on a consensus-binding site on subdomain-1 of actin subunits. Strikingly, the binding of cortactin widens the gap between the two long-pitch filament strands. Although other proteins have been found to alter the structure of the filament, the cortactin-induced conformational change appears unique. The results are consistent with a mechanism whereby alterations of the F-actin structure may facilitate recruitment of the Arp2/3 complex to the 'mother' filament in the cortex of cells. In addition, cortactin may act as a structural adapter protein, stabilizing nascent filament branches while mediating the simultaneous recruitment of Arp2/3 and WASP. |
