title: Interaction between 14-3-3β and PrP influences the dimerization of 14-3-3 and fibrillization of PrP106-126.
abstract: Proteins of the 14-3-3 family are universal participate in multiple cellular processes. However, their exact role in the pathogenesis of prion diseases remains unclear. In this study, we proposed that human PrP was able to form molecular complex with 14-3-3β. The domains responsible for the interactions between PrP and 14-3-3β were mapped at the segments of amino acid (aa) residues 106-126 within PrP and aa 1-38 within 14-3-3β. Homology modeling revealed that the key aa residues for molecular interaction were D22 and D23 in 14-3-3β as well as K110 in PrP. Mutations in these aa residues inhibited the interaction between the two proteins in vitro. Our results also showed that recombinant PrP encouraged 14-3-3β dimer formation, whereas PrP106-126 peptide inhibited it. Recombinant 14-3-3β disaggregated the mature PrP106-126 fibrils in vitro. Moreover, the PrP-14-3-3 protein complexes were observed in the brain tissues of normal and scrapie agent 263K infected hamsters. Colocalization of PrP and 14-3-3 was seen in the cytoplasm of human neuroblastoma cell line SH-SY5Y, as well as human cervical cancer cell line HeLa transiently expressing full-length human PrP. Our current data suggest the neuroprotection of PrPC and neuron damage caused by PrPSc may be associated with their functions of 14-3-3 dimerization regulation.
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Hangzhou), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing 102206, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Han
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Hangzhou), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing 102206, People's Republic of China.
authors.forename: Qin-Qin
authors.initials: QQ
authors.lastname: Song
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Hangzhou), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing 102206, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Hangzhou), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing 102206, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Chemistry and Materials Science, Nanjing Normal University, 122 Ninghai Road, Nanjing 210097, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Hangzhou), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing 102206, People's Republic of China.
authors.forename: Juan
authors.initials: J
authors.lastname: Song
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Hangzhou), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing 102206, People's Republic of China.
authors.forename: Gong-Qi
authors.initials: GQ
authors.lastname: Li
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Hangzhou), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing 102206, People's Republic of China.
authors.forename: Ying-Hui
authors.initials: YH
authors.lastname: Liu
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Hangzhou), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing 102206, People's Republic of China.
authors.forename: Guo-Yong
authors.initials: GY
authors.lastname: Mei
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Hangzhou), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing 102206, People's Republic of China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Shi
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Hangzhou), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing 102206, People's Republic of China.
authors.forename: Chan
authors.initials: C
authors.lastname: Tian
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Hangzhou), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing 102206, People's Republic of China.
authors.forename: Cao
authors.initials: C
authors.lastname: Chen
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Hangzhou), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing 102206, People's Republic of China.
authors.forename: Chen
authors.initials: C
authors.lastname: Gao
authors.affiliation: College of Chemistry and Materials Science, Nanjing Normal University, 122 Ninghai Road, Nanjing 210097, People's Republic of China. Electronic address: zbchem@126.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhao
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases (Hangzhou), National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, 155 Changbai Road, Beijing 102206, People's Republic of China; Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China. Electronic address: dongxp238@sina.com.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Dong
mesh_terms: D048948:14-3-3 Proteins / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D006224:Cricetinae; D019281:Dimerization; D006367:HeLa Cells; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D018620:PrPSc Proteins / Q000378:metabolism; D011328:Prions / Q000737:chemistry* / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D010446:Peptide Fragments; D018620:PrPSc Proteins; D011328:Prions; C082632:prion protein (106-126)
keywords: 14-3-3; Disaggregation; Fibril; PrP; Prion disease