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TitleStructural mechanisms of drebrin-mediated F-actin network modulation.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Year 2026
Publish dateJun 23, 2026
AuthorsW Zhao / L Y Chu / G Abis / F Oozeer / T Mulvaney / N Nagar / M Topf / P R Gordon-Weeks / M R Conte / J Atherton /
PubMed AbstractDrebrin modulates F-actin networks and links them to other intracellular components, regulating crucial processes including neuritogenesis, synaptic plasticity, virus internalisation and cancer ...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.
External linksNat Commun / PubMed:42337253 / PubMed Central
MethodsEM (single particle)
Resolution2.29 - 2.37 Å
Structure data

55893

9tg8

EMDB-55893, PDB-9tg8:
Drebrin actin binding domain 1 conformation A (ABD1a) bound to F-actin
Method: EM (single particle) / Resolution: 2.37 Å

55894

9tg9

EMDB-55894, PDB-9tg9:
Drebrin actin binding domain 1 conformation B (ABD1b) bound to F-actin
Method: EM (single particle) / Resolution: 2.34 Å

55895

9tga

EMDB-55895, PDB-9tga:
Drebrin actin binding domain 2 bound to F-actin
Method: EM (single particle) / Resolution: 2.29 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
  • oryctolagus cuniculus (rabbit)
KeywordsSTRUCTURAL PROTEIN / F-actin binding protein

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