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Acceleration of α‐synuclein aggregation by homologous peptides
Author(s) -
Du Hai-Ning,
Li Hong-Tao,
Zhang Feng,
Lin Xiao-Jing,
Shi Jia-Hao,
Shi Yan-Hong,
Ji Li-Na,
Hu Jun,
Lin Dong-Hai,
Hu Hong-Yu
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.05.050
Subject(s) - peptide , protein superfamily , peptide sequence , chemistry , mutant , alanine , fibril , sequence motif , structural motif , biochemistry , homologous recombination , protein aggregation , valine , amino acid , protein structure , sequence (biology) , biophysics , biology , gene
α‐Synuclein (α‐Syn), amyloid β‐protein and prion protein are among the amyloidogenic proteins that are associated with the neurodegenerative diseases. These three proteins share a homologous region with a consensus sequence mainly consisting of glycine, alanine and valine residues (accordingly named as the GAV motif), which was proposed to be the critical core for the fibrillization and cytotoxicity. To understand the role of the GAV motif in protein amyloidogenesis, we studied the effects of the homologous peptides corresponding to the sequence of GAV motif region (residues 66–74) on α‐Syn aggregation. The result shows that these peptides can promote fibrillization of wild‐type α‐Syn and induce that of the charge‐incorporated mutants but not the GAV‐deficient α‐Syn mutant. The acceleration of α‐Syn aggregation by the homologous peptides is under a sequence‐specific manner. The interplay between the GAV peptide and the core regions in α‐Syn may accelerate the aggregation process and stabilize the fibrils. This finding provides clues for developing peptide mimics that could promote transforming the toxic oligomers or protofibrils into the inert mature fibrils.