High-resolution cryo-EM structure of the F-actin-fimbrin/plastin ABD2 complex

Many actin binding proteins have a modular architecture, and calponin-homology (CH) domains are one such structurally conserved module found in numerous proteins that interact with F-actin. The manner in which CH-domains bind F-actin has been controversial. Using cryo-EM and a single-particle approa...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2008-02, Vol.105 (5), p.1494-1498
Main Authors: Galkin, Vitold E, Orlova, Albina, Cherepanova, Olga, Lebart, Marie-Christine, Egelman, Edward H
Format: Article
Language:English
Subjects:
Actins
Actins - chemistry
Atomic interactions
Binding sites
Biochemistry
Biochemistry, Molecular Biology
Biological Sciences
Biopolymers
Cryoelectron Microscopy
Crystal structure
Crystals
Cytoskeleton
Humans
Life Sciences
Membrane Glycoproteins
Membrane Glycoproteins - chemistry
Microfilament Proteins
Microfilament Proteins - chemistry
Microfilaments
Nucleotides
Phosphoproteins
Phosphoproteins - chemistry
Pixels
Protein Conformation
Protein Structure, Tertiary
Protein subunits
Proteins
Yeasts
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Summary:Many actin binding proteins have a modular architecture, and calponin-homology (CH) domains are one such structurally conserved module found in numerous proteins that interact with F-actin. The manner in which CH-domains bind F-actin has been controversial. Using cryo-EM and a single-particle approach to helical reconstruction, we have generated 12-Å-resolution maps of F-actin alone and F-actin decorated with a fragment of human fimbrin (L-plastin) containing tandem CH-domains. The high resolution allows an unambiguous fit of the crystal structure of fimbrin into the map. The interaction between fimbrin ABD2 (actin binding domain 2) and F-actin is different from any interaction previously observed or proposed for tandem CH-domain proteins, showing that the structural conservation of the CH-domains does not lead to a conserved mode of interaction with F-actin. Both the stapling of adjacent actin protomers and the additional closure of the nucleotide binding cleft in F-actin when the fimbrin fragment binds may explain how fimbrin can stabilize actin filaments. A mechanism is proposed where ABD1 of fimbrin becomes activated for binding a second actin filament after ABD2 is bound to a first filament, and this can explain how mutations of residues buried in the interface between ABD2 and ABD1 can rescue temperature-sensitive defects in actin.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0708667105