Functional domains on chemically modified tau protein.
1. Neurofibrillary tangles present in Alzheimer's disease and, in a lower proportion, in aged brains are formed mainly by paired helical filaments. The microtubule-associated protein tau is a major structural component of these filaments. In order to increase our understanding of the aberrant behaviour of tau protein leading to its assembly into paired helical filaments, studies were carried out using chemical modifications of brain tau protein. 2. Selective carbamoylation of tau with KCNO resulted in an irreversible modification of lysine residues on tau protein. The capacity of chemically modified tau protein to induce tubulin assembly, under standard in vitro microtubule polymerization conditions, decreased gradually in relation to the increase in concentration of the modifying reagent. 3. Interestingly, carbamoylated tau protein exhibited the capacity to self-assemble into polymeric structures resembling those of paired helical filaments, after incubating the modified protein at concentrations higher than 1.0 mg/ml, at 37 degrees C with KCNO. 4. The nature of polymers obtained from cabamoylated tau protein was analyzed by ultrastructural studies. The data provide new clues toward our understanding of the anomalous interactions of tau in Alzheimer's disease.
Farías
G A
GA
International Center for Cancer and Developmental Biology (ICC), Laboratory of Cellular and Molecular Biology, Santiago, Chile.
Vial
C
C
Maccioni
R B
RB
D000215:Acylation; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D006801:Humans; D008239:Lysine; D008854:Microscopy, Electron; D008870:Microtubules / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000737:chemistry*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry; D011108:Polymers; D017434:Protein Structure, Tertiary; D014404:Tubulin / Q000302:isolation & purification / Q000378:metabolism / Q000648:ultrastructure; D016875:tau Proteins / Q000737:chemistry* / Q000187:drug effects / Q000302:isolation & purification / Q000648:ultrastructure
D010446:Peptide Fragments; D011108:Polymers; D014404:Tubulin; D016875:tau Proteins; D008239:Lysine