Inhibition of actin polymerization by a synthetic dodecapeptide patterned on the sequence around the actin-binding site of cofilin

• Published in: The Journal of biological chemistry Vol. 266; no. 16; pp. 10485 - 10489
• Main Authors: YONEZAWA, N, NISHIDA, E, IIDA, K, KUMAGAI, H, YAHARA, I, SAKAI, H
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 05.06.1991
• Subjects: actin; Actin Depolymerizing Factors; Actins - antagonists & inhibitors; Actins - metabolism; Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; Binding and carrier proteins; Biological and medical sciences; Chickens; Cross-Linking Reagents; Electrophoresis, Polyacrylamide Gel; Escherichia coli - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Bacterial; Mammals; Microfilament Proteins; Molecular Sequence Data; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Peptides - pharmacology; Polymers; Proteins; Recombinant Proteins - metabolism; Sequence Homology, Nucleic Acid; Swine; Binding protein; Synthetic product; Structure activity relation; Actins; Polymerization; Contractile protein; Binding site; Inhibition
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)99250-1

Cofilin is an F-actin side-binding and -depolymerizing protein with an apparent molecular mass of 21 kDa. By means of the end label fingerprinting method, the amino acid residue on cofilin sequence cross-linked to actin by zero length cross-linker, 1-ethyl-3-(3-dimethylamino propyl)carbodiimide, was identified as Lys112 and/or Lys114. A synthetic dodecapeptide patterned on the sequence around the actin-cross-linking site of cofilin (Trp104-Met115) inhibited the binding of cofilin to actin. Moreover, the dodecapeptide was found to be a potent inhibitor of actin polymerization. Thus, we conclude that the dodecapeptide sequence constitutes the region essential for the actin-binding and -depolymerizing activity of cofilin. A sequence similar to the dodecapeptide is found in other actin-depolymerizing proteins, destrin, actin-depolymerizing factor, and depactin. Therefore, the dodecapeptide sequence may be a consensus sequence essential for actin-binding and -depolymerizing activity in actin-depolymerizing proteins.