RRC ID 20968
著者 Eckert C, Goretzki A, Faberova M, Kollmar M.
タイトル Conservation and divergence between cytoplasmic and muscle-specific actin capping proteins: insights from the crystal structure of cytoplasmic Cap32/34 from Dictyostelium discoideum.
ジャーナル BMC Struct Biol
Abstract 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.
巻・号 12
ページ 12
公開日 2012-6-1
DOI 10.1186/1472-6807-12-12
PII 1472-6807-12-12
PMID 22657106
PMC PMC3472329
MeSH 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
IF 1.231
引用数 0
WOS 分野 BIOPHYSICS
リソース情報
細胞性粘菌 G20256 G02895