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Structural basis of actin monomer re-charging by cyclase-associated protein

DOI: 10.1038/s41467-018-04231-7 DOI Help

Authors: Tommi Kotila (University of Helsinki) , Konstantin Kogan (University of Helsinki) , Giray Enkavi (University of Helsinki) , Siyang Guo (Brandeis University) , Ilpo Vattulainen (University of Helsinki; Tampere University of Technology) , Bruce L. Goode (Brandeis University) , Pekka Lappalainen (University of Helsinki)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Communications , VOL 9

State: Published (Approved)
Published: May 2018

Open Access Open Access

Abstract: Actin polymerization powers key cellular processes, including motility, morphogenesis, and endocytosis. The actin turnover cycle depends critically on “re-charging” of ADP-actin monomers with ATP, but whether this reaction requires dedicated proteins in cells, and the underlying mechanism, have remained elusive. Here we report that nucleotide exchange catalyzed by the ubiquitous cytoskeletal regulator cyclase-associated protein (CAP) is critical for actin-based processes in vivo. We determine the structure of the CAP–actin complex, which reveals that nucleotide exchange occurs in a compact, sandwich-like complex formed between the dimeric actin-binding domain of CAP and two ADP-actin monomers. In the crystal structure, the C-terminal tail of CAP associates with the nucleotide-sensing region of actin, and this interaction is required for rapid re-charging of actin by both yeast and mammalian CAPs. These data uncover the conserved structural basis and biological role of protein-catalyzed re-charging of actin monomers.

Journal Keywords: Actin; X-ray crystallography

Subject Areas: Biology and Bio-materials

Instruments: I04-Macromolecular Crystallography