Tertiary structure of destrin and structural similarity between two actin-regulating protein families.
Destrin is an isoprotein of cofilin that regulates actin cytoskeleton in various eukaryotes. We determined the tertiary structure of destrin by triple-resonance multidimensional nuclear magnetic resonance. In spite of there being no significant amino acid sequence homology, we found that the folding of destrin was strikingly similar to that of repeated segments in the gelsolin family, which resulted in a new protein fold group. Sequential dissimilarity of the actin-binding helix of destrin to that of gelsolin explains the Ca2+-independent actin-binding of destrin. Possible mechanisms of phosphorylation-sensitive phosphoinositide-competitive actin binding, of pH-dependent filament severing, and of nuclear translocation with actin in response to stresses, are discussed on the basis of the tertiary structure.
Hatanaka
H
H
Tokyo Metropolitan Institute of Medical Science, Japan.
Ogura
K
K
Moriyama
K
K
Ichikawa
S
S
Yahara
I
I
Inagaki
F
F
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000737:chemistry / Q000378:metabolism; D001667:Binding, Competitive / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D003598:Cytoskeletal Proteins; D051345:Destrin; D018260:Gelsolin / Q000737:chemistry* / Q000378:metabolism; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D007091:Image Processing, Computer-Assisted; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010716:Phosphatidylinositols / Q000378:metabolism; D010766:Phosphorylation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid
D051339:Actin Depolymerizing Factors; D000199:Actins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D051345:Destrin; D018260:Gelsolin; D010716:Phosphatidylinositols; D002118:Calcium