7PDZ

Structure of capping protein bound to the barbed end of a cytoplasmic actin filament

Summary for 7PDZ

• Entry DOI: 10.2210/pdb7pdz/pdb
• EMDB information: 13343
• Related PRD ID: PRD_002307
• Descriptor: Isoform 2 of F-actin-capping protein subunit beta, F-actin-capping protein subunit alpha-1, Actin, cytoplasmic 1, ... (7 entities in total)
• Functional Keywords: cytoskeleton, cell-shape remodelling, barbed end, structural protein
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 13
• Total formula weight: 321557.97

Authors

Funk, J.,Merino, F.,Schacks, M.,Rottner, K.,Raunser, S.,Bieling, P. (deposition date: 2021-08-09, release date: 2021-09-01, Last modification date: 2021-10-06)

Primary citation

Funk, J.,Merino, F.,Schaks, M.,Rottner, K.,Raunser, S.,Bieling, P.
A barbed end interference mechanism reveals how capping protein promotes nucleation in branched actin networks.
Nat Commun, 12:5329-5329, 2021

PubMed Abstract: Heterodimeric capping protein (CP/CapZ) is an essential factor for the assembly of branched actin networks, which push against cellular membranes to drive a large variety of cellular processes. Aside from terminating filament growth, CP potentiates the nucleation of actin filaments by the Arp2/3 complex in branched actin networks through an unclear mechanism. Here, we combine structural biology with in vitro reconstitution to demonstrate that CP not only terminates filament elongation, but indirectly stimulates the activity of Arp2/3 activating nucleation promoting factors (NPFs) by preventing their association to filament barbed ends. Key to this function is one of CP's C-terminal "tentacle" extensions, which sterically masks the main interaction site of the terminal actin protomer. Deletion of the β tentacle only modestly impairs capping. However, in the context of a growing branched actin network, its removal potently inhibits nucleation promoting factors by tethering them to capped filament ends. End tethering of NPFs prevents their loading with actin monomers required for activation of the Arp2/3 complex and thus strongly inhibits branched network assembly both in cells and reconstituted motility assays. Our results mechanistically explain how CP couples two opposed processes-capping and nucleation-in branched actin network assembly.

PubMed: 34504078
DOI: 10.1038/s41467-021-25682-5

Experimental method

ELECTRON MICROSCOPY (3.8 Å)