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Publication Abstract from PubMed

Gelsolin superfamily proteins, consisting of multiple domains (usually six), sever actin filaments and cap the barbed ends in a Ca(2+)-dependent manner. Two types of evolutionally conserved Ca(2+)-binding sites have been identified in this family; type-1 (between gelsolin and actin) and type-2 (within the gelsolin domain). Fragmin, a member in the slime mold Physarum polycephalum, consists of three domains (F1-F3) that are highly similar to the N-terminal half of mammalian gelsolin (G1-G3). Despite their similarities, the two proteins exhibit a significant difference in the Ca(2+) dependency; F1-F3 absolutely requires Ca(2+) for the filament severing whereas G1-G3 does not. In this study, we examined the strong dependency of fragmin on Ca(2+) using biochemical and structural approaches. Our co-sedimentation assay demonstrated that Ca(2+) significantly enhanced the binding of F2-F3 to actin. We determined the crystal structure of F2-F3 in the presence of Ca(2+). F2-F3 binds a total of three calcium ions; while two are located in type-2 sites within F2 or F3, the remaining one resides between the F2 long helix and the F3 short helix. The inter-domain Ca(2+)-coordination appears to stabilize F2-F3 in a closely packed configuration. Notably, the F3 long helix exhibits a bent conformation which is different from the straight G3 long helix in the presence of Ca(2+). Our results provide the first structural evidence for the existence of an unconventional Ca(2+)-binding site in the gelsolin superfamily proteins.

Novel inter-domain Ca(2+)-binding site in the gelsolin superfamily protein fragmin.,Takeda S, Fujiwara I, Sugimoto Y, Oda T, Narita A, Maeda Y J Muscle Res Cell Motil. 2019 Dec 20. pii: 10.1007/s10974-019-09571-5. doi:, 10.1007/s10974-019-09571-5. PMID:31863323^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.