TY - JOUR
T1 - Structural stability of paired helical filaments requires microtubule-binding domains of Tau
T2 - A model for self-association
AU - Ksiezak-Reding, Hanna
AU - Yen, Shu Hui
N1 - Funding Information:
We thank Dr. Virginia Lee for providing antibodies Tau 14 and Tau 46, Dr. David Martin (Genentech Inc., San Francisco, CA) for providing antiserum AH-l, Dr. Tony Crowther for helpful discussion, and Dr. Wan-Kyng Liu and Alex Crowe for their comments on the manuscript. The help of the laboratory for Electron Microscopy, headed by Yvonne Kress, is greatly appreciated. This work was supported by National Institutes of Health grants AG1136, AC4145, and AGO6803 and by a grant from the Alzheimer’s Disease and Related Disorders Association.
PY - 1991/5
Y1 - 1991/5
N2 - Highly purified and SDS-soluble paired helical filaments (PHFs) were immunogold labeled and immunoblotted with antibodies to tau: Tau 14 (N-terminal half), AH-1 (microtubule-binding domain), and Tau 46 (C-terminal end). The main component of PHFs was modified tau of 68, 64, and 60 kd, also called A68 or PHF-tau. Trypsin digestion reduced the maximum width of PHFs by 10%-20%, increased aggregation of filaments, and abolished the binding of Tau 14, but had no effect on the binding of AH-1. The smallest tau-reactive tryptic fragments were 13 and 7-8 kd, positive with AH-1, and negative with Tau 46. Our results and the model of Crowther and Wischik suggest that by self-association and anti-parallel arrangement of the microtubule-binding domains, PHF-tau forms the backbone of PHFs.
AB - Highly purified and SDS-soluble paired helical filaments (PHFs) were immunogold labeled and immunoblotted with antibodies to tau: Tau 14 (N-terminal half), AH-1 (microtubule-binding domain), and Tau 46 (C-terminal end). The main component of PHFs was modified tau of 68, 64, and 60 kd, also called A68 or PHF-tau. Trypsin digestion reduced the maximum width of PHFs by 10%-20%, increased aggregation of filaments, and abolished the binding of Tau 14, but had no effect on the binding of AH-1. The smallest tau-reactive tryptic fragments were 13 and 7-8 kd, positive with AH-1, and negative with Tau 46. Our results and the model of Crowther and Wischik suggest that by self-association and anti-parallel arrangement of the microtubule-binding domains, PHF-tau forms the backbone of PHFs.
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U2 - 10.1016/0896-6273(91)90169-Z
DO - 10.1016/0896-6273(91)90169-Z
M3 - Article
C2 - 1709023
AN - SCOPUS:0025852163
SN - 0896-6273
VL - 6
SP - 717
EP - 728
JO - Neuron
JF - Neuron
IS - 5
ER -