Gelsolin

Mammalian protein found in Homo sapiens

Gelsolin is an actin binding protein that is a key regulator of actin filament assembly and disassembly. Gelsolin is one of the most potent members of the actin severing gelsolin/villin superfamily, as it severs with nearly 100% efficiency. Cellular gelsolin, found within the cytosol and mitochondria, has a closely related secreted form, Plasma gelsolin, that contains an additional 24 AA N terminal extension. Plasma gelsolin's ability to sever actin filaments helps the body recover from disease and injury that leaks cellular actin into the blood. Additionally it plays important roles in host innate immunity, activating macrophages and localizing of inflammation.

Gelsolin is an 82 kD protein with six homologous subdomains, referred to as S1 S6. Each subdomain is composed of a five stranded β sheet, flanked by two α helices, one positioned perpendicular with respect to the strands and one positioned parallel. The β sheets of the three N terminal subdomains (S1 S3) join to form an extended β sheet, as do the β sheets of the C terminal subdomains (S4 S6).

Among the lipid binding actin regulatory proteins, gelsolin (like cofilin) preferentially binds polyphosphoinositide (PPI). The binding sequences in gelsolin closely resemble the motifs in the other PPI binding proteins. The C terminal end detects the calcium concentration within the cell. When there is no Ca2+ present, the tail of S6 shields the actin binding sites on one of S2's helices. Gelsolin also inhibits apoptosis by stabilizing the mitochondria. Actin can be cross linked into a gel by actin cross linking proteins. Gelsolin can turn this gel into a sol, hence the name gelsolin.

Research in mice suggests that gelsolin, like other actin severing proteins, is not expressed to a significant degree until after the early embryonic stage—approximately 2 weeks in murine embryos. In adult specimens, however, gelsolin is particularly important in motile cells, such as blood platelets. Mice with null gelsolin coding genes undergo normal embryonic development, but the deformation of their blood platelets reduced their motility, resulting in a slower response to wound healing.

Sequence comparisons indicate an evolutionary relationship between gelsolin, villin, fragmin, and severin. Six large repeating segments occur in gelsolin and villin, and 3 similar segments in severin and fragmin. The multiple repeats are related in structure (but barely in sequence) to the ADF H domain, forming a superfamily The family appears to have evolved from an ancestral sequence of 120 to 130 amino acid residues.