Interaction of substance P with tubulin.
Binding of the peptide neurotransmitter substance P to brain tubulin in vitro inhibits self-assembly of the protein into microtubules and disrupts preassembled microtubules. This cooperative inhibition of the maximum extent of self-assembly by substance P is explicable in terms of preferential binding to the protomer state as compared to the polymer state of tubulin. The inhibition is relieved by the microtubule-associated protein MAP2, which evidently acts in a mixed competitive-noncompetitive fashion. Substance P interacts directly with the isolated C-terminal 4-kDa peptide fragment of tubulin, which appears to contain the specific binding area for MAP2, but is without effect on the self-assembly of the larger (48-kDa) part of the tubulin molecule called S-tubulin. The results are consistent with the C-terminal fragment having a binding site for the cationic substance P as well as for MAP2. However, factors other than electrostatic interaction must be operative, since the sulfoxide of substance P, a derivative with oxidized methionine but similar electrostatic characteristics, is inactive in inhibiting the extent of microtubule assembly.
R B
RB
Maccioni
J R
JR
Cann
J M
JM
Stewart
D000818:Animals; D001667:Binding, Competitive; D004563:Electrochemistry; D004586:Electrophoresis / Q000379:methods; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D009391:Nephelometry and Turbidimetry; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D012756:Sheep; D013373:Substance P / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism*; D014461:Ultracentrifugation; D016875:tau Proteins
D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; D014404:Tubulin; D016875:tau Proteins; D013373:Substance P