Human tau protein forms complex with PrP and some GSS- and fCJD-related PrP mutants possess stronger binding activities with tau in vitro.
Microtubule associated protein tau is considered to play roles in some types of human transmissible spongiform encephalopathies (TSE). In this study, the full-length and several truncated human tau proteins were expressed from E. coli and purified. Using GST pull down, co-immunoprecipitation assay and tau-coated ELISA, the molecular interaction between tau protein and PrP was confirmed in the context of the full-length human tau. The N terminus (amino acids 1-91) and tandem repeats region (amino acids 186-283) of tau protein were responsible for the interaction with PrP. The octapeptide repeats within PrP directly affected the binding activity of PrP with tau. GSS-related mutant PrP102L and fCJD- related mutants with two and seven extra octarepeats showed more active binding capacity with tau than wild-type PrP. The molecular interactions between PrP and tau protein highlight a potential role of tau in the biological function of PrP and the pathogenesis of TSE.
State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Ying-Xin Rd 100, Beijing 100052, PR China.
Xiao-Fan
XF
Wang
Chen-Fang
CF
Dong
Jin
J
Zhang
Yan-Zhen
YZ
Wan
Feng
F
Li
Yin-Xia
YX
Huang
Lu
L
Han
Bing
B
Shan
Chen
C
Gao
Jun
J
Han
Xiao-Ping
XP
Dong
D045744:Cell Line, Tumor; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism*; D016098:Gerstmann-Straussler-Scheinker Disease / Q000378:metabolism*; D006801:Humans; D050505:Mutant Proteins / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D018621:PrPC Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
D050505:Mutant Proteins; D010455:Peptides; D018621:PrPC Proteins; D011993:Recombinant Fusion Proteins; D016875:tau Proteins