Synuclein proteins of the pufferfish Fugu rubripes: sequences and functional characterization.
In humans, three genes encode the related alpha-, beta-, and gamma-synucleins, which function as lipid-binding proteins in vitro. They are being widely studied, mainly because of the central involvement of alpha-synuclein in a number of neurodegenerative diseases, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. In these diseases, the normally soluble alpha-synuclein assembles into abnormal filaments. Here, we have identified and characterized the synuclein gene family from the pufferfish Fugu rubripes. It consists of four genes, which encode alpha-, beta-, gamma1-, and gamma2-synucleins. They range from 113 to 127 amino acids in length and share many of the characteristics of human synucleins, including the presence of imperfect amino-terminal repeats of 11 amino acids, a hydrophobic middle region, and a negatively charged carboxy-terminus. All four synucleins are expressed in the Fugu brain. Recombinant Fugu synucleins exhibited differential liposome binding, which was strongest for alpha-synuclein, followed by beta-, gamma2-, and gamma1-synucleins. In assembly experiments, Fugu alpha-, gamma1-, and gamma2-synucleins formed filaments more readily than human alpha-synuclein. Fugu beta-synuclein, by contrast, failed to assemble in bulk. Filament assembly of synucleins was directly proportional to their degree of hydrophobicity and their tendency to form beta-sheet structure, and correlated inversely with their net charge.
MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom.
Hirotaka
H
Yoshida
Molly
M
Craxton
Ross
R
Jakes
Shahin
S
Zibaee
Richard
R
Tavaré
Graham
G
Fraser
Louise C
LC
Serpell
Bazbek
B
Davletov
R Anthony
RA
Crowther
Michel
M
Goedert
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D051843:Synucleins; D023741:Takifugu / Q000235:genetics* / Q000502:physiology; D013997:Time Factors
D018076:DNA, Complementary; D008081:Liposomes; D011994:Recombinant Proteins; D051843:Synucleins