tailieunhanh - Báo cáo khoa học: Linkage-dependent contribution of repeat peptides to self-aggregation of three- or four-repeat microtubulebinding domains in tau protein

Although one of the priorities in Alzheimer’s research is to clarify the fila-ment formation mechanism for the tau protein, it is still unclear how it is transformed from a normal structure in a neuron. To examine the linkage-dependent contribution of each repeat peptide (R1–R4) to filament forma- | ỊFEBS Journal Linkage-dependent contribution of repeat peptides to self-aggregation of three- or four-repeat microtubulebinding domains in tau protein Kayoko Okuyama1 Chisato Nishiura1 Fumie Mizushima1 Katsuhiko Minoura1 Miho Sumida2 Taizo Taniguchi2 Koji Tomoo1 and Toshimasa Ishida1 1 Osaka University of PharmaceuticalSciences Takatsuki Osaka Japan 2 Behavioraland MedicalSciences Research Consortium Akashi Hyogo Japan Keywords aggregation CD fluorescence repeat linkage dependence tau microtubule-binding domain Correspondence K. Minoura or K. Tomoo Research Center Osaka University of Pharmaceutical Sciences 4-20-1 Nasahara Takatsuki Osaka 569-1094 Japan Fax 81 726 90 1039 Tel 81 726 90 1068 E-mail minoura@ tomoo@ Received 10 October 2007 revised 27 December 2007 accepted 28 January 2008 doi Although one of the priorities in Alzheimer s research is to clarify the filament formation mechanism for the tau protein it is still unclear how it is transformed from a normal structure in a neuron. To examine the linkagedependent contribution of each repeat peptide R1-R4 to filament formation of the three- or four-repeat microtubule-binding domain MBD in the tau protein four two-repeat peptides R12 R13 R23 and R34 and two three-repeat peptides R123 and R234 were prepared and their in vitro self-aggregation was investigated by thioflavin S fluorescence and circular dichroism measurements and by electron microscopy in neutral buffer pH . Comparison of these aggregation behaviors with previous results for single-repeat peptides and wild-type 3RMBD R134 and 4RMBD R1234 indicated that a the two-repeat R23 not the R2 or R3 single repeat forms the core structure in self-aggregation of 4RMBD whereas that of 3RMBD comprises the R3 single repeat b co-existence of R1 and R4 repeats is necessary for the aggregation behavior inherent in 3RMBD and 4RMBD whereas the R1 or R4 repeat alone functions as a repressor or modifier of