G- to F-actin modulation by a single amino acid substitution in the actin binding site of actobindin and thymosin beta 4.
The actin binding sites of actobindin and thymosin beta 4, two small polypeptides that inhibit actin polymerization by interacting with monomeric actin, have been localized using peptide mimetics. Both sites are functionally similar and extend over 20 residues and are located in the NH2-terminus of the polypeptides. They can be dissected into two functional entities: a conserved hexapeptide motif (LKHAET or LKKTET), which forms the major contact site through electrostatic interactions with actin, and a non-conserved NH2-terminal segment preceding the motif, which exerts the inhibitory activity on actin polymerization probably by steric hindrance. The introduction of a glutamic acid at the third position in the motif, creating LKEAET or LKETET sequences, which are similar to those found in some F-actin binding proteins, converts the peptide's inhibitory phenotype into an F-actin stimulatory property. These results allow the proposal of a simple model for G- to F-actin modulation.
Vancompernolle
K
K
Laboratory of Physiological Chemistry, University of Ghent, Belgium.
Goethals
M
M
Huet
C
C
Louvard
D
D
Vandekerckhove
J
J
D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D009132:Muscles / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D017354:Point Mutation; D011487:Protein Conformation; D015800:Protozoan Proteins; D011817:Rabbits; D013947:Thymosin / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism; D000099201:Thymosin beta(4)
D000199:Actins; D000596:Amino Acids; D002352:Carrier Proteins; D008840:Microfilament Proteins; D009842:Oligopeptides; D015800:Protozoan Proteins; D013947:Thymosin; D000099201:Thymosin beta(4); C050869:actobindin protein, Acanthamoeba