The microtubule-associated protein tau forms a triple-stranded left-hand helical polymer.
High resolution transmission electron microscopy (TEM) has shown that bovine tau are 2.1 +/- 0.2-nm diameter filaments which are triple-stranded left-hand helical structures composed of three 1.0 +/- 0.2-nm strands. The reported amino acid sequence of human and bovine tau have been computer processed to predict secondary structure. Within the constraints imposed by the images, the secondary structure models and other structural information have been used to calculate tau's maximum and minimum length. The length calculations and secondary structure form the basis for image interpretation. This work indicates that each approximately 1.0-nm strand is a tau polypeptide chain and that the approximately 2.1-nm filament is composed of three separate tau chains (tau3). Bovine tau length measurements indicate that tau trimer filaments are generally longer than a fully extended tau monomer. These measurements indicate that each trimer, tau3, is joined with other trimers to form long tau polymers, (tau3)n. An inverse temperature transition has been found in the circular dichroism spectrum of tau indicating that its structure is less ordered below 20 degrees C and more ordered at 37 degrees C. The implications of this phenomenon with respect to tau's temperature-dependent ability to reconstitute microtubules is discussed and a mechanism for the possible abnormal aggregation of tau into neurofibrillary tangles in Alzheimer's disease is proposed.
Department of Biological Sciences, Dartmouth College, Hanover, New Hampshire 03755.
G C
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Ruben
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Iqbal
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Grundke-Iqbal
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Wisniewski
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Ciardelli
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Johnson
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D004549:Elastin / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D005612:Freeze Drying; D006801:Humans; D008854:Microscopy, Electron; D008870:Microtubules / Q000737:chemistry / Q000648:ultrastructure; D008961:Models, Structural; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid; D016875:tau Proteins / Q000737:chemistry / Q000302:isolation & purification / Q000648:ultrastructure*
D016875:tau Proteins; D004549:Elastin