8TAH

Cryo-EM structure of Cortactin-bound to Arp2/3 complex

Summary for 8TAH

• Entry DOI: 10.2210/pdb8tah/pdb
• EMDB information: 41135
• Descriptor: Actin-related protein 3, ADENOSINE-5'-TRIPHOSPHATE, Actin-related protein 2, ... (10 entities in total)
• Functional Keywords: complex, migration, actin, cytoskeleton, contractile protein
• Biological source: Mus musculus (house mouse); More
• Total number of polymer chains: 8
• Total formula weight: 234569.40

Authors

Fregoso, F.E.,van Eeuwen, T.,Dominguez, R. (deposition date: 2023-06-27, release date: 2023-09-27, Last modification date: 2024-01-31)

Primary citation

Fregoso, F.E.,Boczkowska, M.,Rebowski, G.,Carman, P.J.,van Eeuwen, T.,Dominguez, R.
Mechanism of synergistic activation of Arp2/3 complex by cortactin and WASP-family proteins.
Nat Commun, 14:6894-6894, 2023

PubMed Abstract: Cortactin coactivates Arp2/3 complex synergistically with WASP-family nucleation-promoting factors (NPFs) and stabilizes branched networks by linking Arp2/3 complex to F-actin. It is poorly understood how cortactin performs these functions. We describe the 2.89 Å resolution cryo-EM structure of cortactin's N-terminal domain (Cort) bound to Arp2/3 complex. Cortactin binds Arp2/3 complex through an inverted Acidic domain (D20-V29), which targets the same site on Arp3 as the Acidic domain of NPFs but with opposite polarity. Sequences N- and C-terminal to cortactin's Acidic domain do not increase its affinity for Arp2/3 complex but contribute toward coactivation with NPFs. Coactivation further increases with NPF dimerization and for longer cortactin constructs with stronger binding to F-actin. The results suggest that cortactin contributes to Arp2/3 complex coactivation with NPFs in two ways, by helping recruit the complex to F-actin and by stabilizing the short-pitch (active) conformation, which are both byproducts of cortactin's core function in branch stabilization.

PubMed: 37898612
DOI: 10.1038/s41467-023-42229-y

Experimental method

ELECTRON MICROSCOPY (2.89 Å)