Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases.
Four inherited neurodegenerative diseases are linked to abnormally expanded repeats of glutamine residues in the affected proteins. Molecular modeling followed by optical, electron, and x-ray diffraction studies of a synthetic poly(L-glutamine) shows that it forms beta-sheets strongly held together by hydrogen bonds. Glutamine repeats may function as polar zippers, for example, by joining specific transcription factors bound to separate DNA segments. Their extension may cause disease either by increased, nonspecific affinity between such factors or by gradual precipitation of the affected proteins in neurons.
Perutz
M F
MF
Medical Research Council Laboratory of Molecular Biology, Cambridge, England.
Johnson
T
T
Suzuki
M
M
Finch
J T
JT
D000595:Amino Acid Sequence; D005799:Genes, Dominant; D005973:Glutamine / Q000737:chemistry*; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000209:etiology*; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D009134:Muscular Atrophy, Spinal / Q000209:etiology*; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D009687:Nuclear Proteins / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011944:Receptors, Androgen / Q000737:chemistry*; D012091:Repetitive Sequences, Nucleic Acid; D013132:Spinocerebellar Degenerations / Q000209:etiology*
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011944:Receptors, Androgen; D005973:Glutamine