6FM2

CARP domain of mouse cyclase-associated protein 1 (CAP1) bound to ADP-actin

Summary for 6FM2

• Entry DOI: 10.2210/pdb6fm2/pdb
• Descriptor: Actin, alpha skeletal muscle, Adenylyl cyclase-associated protein 1, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: complex, actin cytoskeleton, nucleotide exchange, actin turnover, structural protein
• Biological source: Mus musculus (Mouse); More
• Cellular location: Cytoplasm, cytoskeleton: P68135; Cell membrane ; Peripheral membrane protein : P40124
• Total number of polymer chains: 2
• Total formula weight: 59846.18

Authors

Kotila, T.M.,Kogan, K.,Lappalainen, P. (deposition date: 2018-01-30, release date: 2018-05-16, Last modification date: 2024-01-17)

Primary citation

Kotila, T.,Kogan, K.,Enkavi, G.,Guo, S.,Vattulainen, I.,Goode, B.L.,Lappalainen, P.
Structural basis of actin monomer re-charging by cyclase-associated protein.
Nat Commun, 9:1892-1892, 2018

PubMed 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.

PubMed: 29760438
DOI: 10.1038/s41467-018-04231-7

Experimental method

X-RAY DIFFRACTION (2.8 Å)