9TGA

Drebrin actin binding domain 2 bound to F-actin

Summary for 9TGA

• Entry DOI: 10.2210/pdb9tga/pdb
• EMDB information: 55895
• Descriptor: Drebrin, Actin, alpha skeletal muscle, ADENOSINE-5'-DIPHOSPHATE, ... (5 entities in total)
• Functional Keywords: f-actin binding protein, structural protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 111311.79

Authors

Zhao, W.,Abis, G.,Oozeer, F.,Mulvaney, T.,Nagar, N.,Topf, M.,Gordon-Weeks, P.R.,Conte, M.R.,Atherton, J. (deposition date: 2025-11-28, release date: 2026-09-02)

Primary citation

Zhao, W.,Chu, L.Y.,Abis, G.,Oozeer, F.,Mulvaney, T.,Nagar, N.,Topf, M.,Gordon-Weeks, P.R.,Conte, M.R.,Atherton, J.
Structural mechanisms of drebrin-mediated F-actin network modulation.
Nat Commun, 17:-, 2026

PubMed Abstract: Drebrin modulates F-actin networks and links them to other intracellular components, regulating crucial processes including neuritogenesis, synaptic plasticity, virus internalisation and cancer invasion. Using single-particle cryo-EM we characterise drebrin's interaction with F-actin through two separate conserved actin binding domains (ABD1 and ABD2), revealing structural bases for its F-actin-modulating properties. We describe a multimodal interaction where drebrin's ABD1 can adopt two conformations and a long flexible loop connecting to ABD2 allows the two ABDs to occupy multiple relative positions along F-actin. The flexible loop connecting the two ABDs also confers some propensity to loosely bundle F-actin. Drebrin's ABDs bind across multiple actin protomers and their subdomains and modify the longitudinal inter-protomer interface, explaining its F-actin stabilising properties. Furthermore, we show drebrin's binding site on F-actin is shared with other critical actin-binding and regulatory proteins, explaining their competitive displacement.

PubMed: 42337253
DOI: 10.1038/s41467-026-74543-6

Experimental method

ELECTRON MICROSCOPY (2.29 Å)