Acceleration of alpha-synuclein aggregation by homologous peptides.
alpha-Synuclein (alpha-Syn), amyloid beta-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 alpha-Syn aggregation. The result shows that these peptides can promote fibrillization of wild-type alpha-Syn and induce that of the charge-incorporated mutants but not the GAV-deficient alpha-Syn mutant. The acceleration of alpha-Syn aggregation by the homologous peptides is under a sequence-specific manner. The interplay between the GAV peptide and the core regions in alpha-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.
Du
Hai-Ning
HN
Key Laboratory of Proteomics, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Li
Hong-Tao
HT
Zhang
Feng
F
Lin
Xiao-Jing
XJ
Shi
Jia-Hao
JH
Shi
Yan-Hong
YH
Ji
Li-Na
LN
Hu
Jun
J
Lin
Dong-Hai
DH
Hu
Hong-Yu
HY
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D005998:Glycine / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018625:Microscopy, Atomic Force; D009154:Mutation / Q000235:genetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation / Q000187:drug effects; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D010455:Peptides; D051844:alpha-Synuclein; D005998:Glycine