molecular interaction of tppp with prp antagonized the cytoprp-induced disruption of microtubule structures and cytotoxicity分子间相互作用与prp tppp引起cytoprp-induced破坏微管的结构和细胞毒性.pdfVIP

Molecular Interaction of TPPP with PrP Antagonized the CytoPrP-Induced Disruption of Microtubule Structures and Cytotoxicity 1,2 1 1 1 1 1 1 Rui-Min Zhou , Yuan-Yuan Jing , Yan Guo , Chen Gao , Bao-Yun Zhang , Cao Chen , Qi Shi , 1 1 1 1 2 1 Chan Tian , Zhao-Yun Wang , Han-Shi Gong , Jun Han , Bian-Li Xu , Xiao-Ping Dong * 1 State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People’s Republic of China, 2 Henan Provincial Center for Disease Control and Prevention, Zhengzhou, Henan Province, People’s Republic of China Abstract Background: Tubulin polymerization promoting protein/p25 (TPPP/p25), known as a microtubule-associated protein (MAP), is a brain-specific unstructured protein with a physiological function of stabilizing cellular microtubular ultrastructures. Whether TPPP involves in the normal functions of PrP or the pathogenesis of prion disease remains unknown. Here, we proposed the data that TPPP formed molecular complex with PrP. We also investigated its influence on the aggregation of PrP and fibrillization of PrP106–126 in vitro, its antagonization against the disruption of microtubule structures and cytotoxicity of cytosolic PrP in cells, and its alternation in the brains of scrapie-infected experimental hamsters. Methodology/Principal Findings: Using pull-down and immunoprecipitation assays, distinct molecular interaction between TPPP and PrP were identified and the segment of TPPP spanning residues 100–219 and the segment