Tau protein binds to microtubules through a flexible array of distributed weak sites.
Tau protein plays a role in the extension and maintenance of neuronal processes through a direct association with microtubules. To characterize the nature of this association, we have synthesized a collection of tau protein fragments and studied their binding properties. The relatively weak affinity of tau protein for microtubules (approximately 10(-7) M) is concentrated in a large region containing three or four 18 amino acid repeated binding elements. These are separated by apparently flexible but less conserved linker sequences of 13-14 amino acids that do not bind. Within the repeats, the binding energy for microtubules is delocalized and derives from a series of weak interactions contributed by small groups of amino acids. These unusual characteristics suggest tau protein can assume multiple conformations and can pivot and perhaps migrate on the surface of the microtubule. The flexible structure of the tau protein binding interaction may allow it to be easily displaced from the microtubule lattice and may have important consequences for its function.
Department of Biochemistry, University of California, San Francisco 94143-0448.
K A
KA
Butner
M W
MW
Kirschner
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D002417:Cattle; D007700:Kinetics; D008870:Microtubules / Q000378:metabolism*; D008961:Models, Structural; D008969:Molecular Sequence Data; D009841:Oligonucleotides; D010957:Plasmids; D011487:Protein Conformation; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D013816:Thermodynamics; D014158:Transcription, Genetic; D014404:Tubulin / Q000302:isolation & purification / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*
D009841:Oligonucleotides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014404:Tubulin; D016875:tau Proteins