Conservation and divergence between cytoplasmic and muscle-specific actin capping proteins: insights from the crystal structure of cytoplasmic Cap32/34 from Dictyostelium discoideum

BMC Struct Biol. 2012 Jun 1:12:12. doi: 10.1186/1472-6807-12-12.


Background: Capping protein (CP), also known as CapZ in muscle cells and Cap32/34 in Dictyostelium discoideum, plays a major role in regulating actin filament dynamics. CP is a ubiquitously expressed heterodimer comprising an α- and β-subunit. It tightly binds to the fast growing end of actin filaments, thereby functioning as a "cap" by blocking the addition and loss of actin subunits. Vertebrates contain two somatic variants of CP, one being primarily found at the cell periphery of non-muscle tissues while the other is mainly localized at the Z-discs of skeletal muscles.

Results: To elucidate structural and functional differences between cytoplasmic and sarcomercic CP variants, we have solved the atomic structure of Cap32/34 (32=β- and 34=α-subunit) from the cellular slime mold Dictyostelium at 2.2 Å resolution and compared it to that of chicken muscle CapZ. The two homologs display a similar overall arrangement including the attached α-subunit C-terminus (α-tentacle) and the flexible β-tentacle. Nevertheless, the structures exhibit marked differences suggesting considerable structural flexibility within the α-subunit. In the α-subunit we observed a bending motion of the β-sheet region located opposite to the position of the C-terminal β-tentacle towards the antiparallel helices that interconnect the heterodimer. Recently, a two domain twisting attributed mainly to the β-subunit has been reported. At the hinge of these two domains Cap32/34 contains an elongated and highly flexible loop, which has been reported to be important for the interaction of cytoplasmic CP with actin and might contribute to the more dynamic actin-binding of cytoplasmic compared to sarcomeric CP (CapZ).

Conclusions: The structure of Cap32/34 from Dictyostelium discoideum allowed a detailed analysis and comparison between the cytoplasmic and sarcomeric variants of CP. Significant structural flexibility could particularly be found within the α-subunit, a loop region in the β-subunit, and the surface of the α-globule where the amino acid differences between the cytoplasmic and sarcomeric mammalian CP are located. Hence, the crystal structure of Cap32/34 raises the possibility of different binding behaviours of the CP variants toward the barbed end of actin filaments, a feature, which might have arisen from adaptation to different environments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Capping Proteins / chemistry*
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • CapZ Actin Capping Protein / chemistry
  • Chickens
  • Conserved Sequence*
  • Crystallography, X-Ray
  • Cytoplasm / metabolism*
  • Dictyostelium / chemistry*
  • Lipids
  • Microfilament Proteins / chemistry*
  • Models, Molecular
  • Molecular Sequence Data
  • Muscles / metabolism*
  • Organ Specificity
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Protozoan Proteins / chemistry*
  • Sequence Alignment


  • Actin Capping Proteins
  • CapZ Actin Capping Protein
  • Lipids
  • Microfilament Proteins
  • Protein Subunits
  • Protozoan Proteins
  • cap32-34 protein, Dictyostelium