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Aberrant guanosine triphosphate–beta‐tubulin interaction in Alzheimer's disease
Author(s) -
Khatoon Sabiha,
Campbell Susan R.,
Haley Boyd E.,
Slevin John T.
Publication year - 1989
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410260205
Subject(s) - gtp' , tubulin , guanosine , guanine , guanosine triphosphate , nucleotide , microtubule , alzheimer's disease , guanosine diphosphate , chemistry , biochemistry , biology , microbiology and biotechnology , medicine , enzyme , disease , gene
Guanosine triphosphate (GTP) is an absolute requirement for tubulin polymerization in situ. The nucleotide photoaffinity probe 8‐azidoguanosine 5′‐triphosphate (8N 3 GTP) has been shown to be a biological mimic of GRP in this system and, also, an effective active site probe of the exchangeable GRP binding site. Using [ 32 P]8N 3 GTP we demonstrate that the exchangeable GTP site of the beta subunit of tubulin is available to added guanine nucleotide in normal aged brain homogenates, whereas it is variably unavailable in Alzheimer's diseased brain. Inability of 8N 3 GTP to photolabel beta tubulin appears to be associated with neurofibrillary tangle density. These results support the hypothesis that microtubule formation is abnormal in brains affected by Alzheimer's disease.