Peptides containing glutamine repeats as substrates for transglutaminase-catalyzed cross-linking: Relevance to diseases of the nervous system
AUTOR(ES)
Kahlem, P.
FONTE
The National Academy of Sciences of the USA
RESUMO
Many proteins contain reiterated glutamine residues, but polyglutamine of excessive length may result in human disease by conferring new properties on the protein containing it. One established property of a glutamine residue, depending on the nature of the flanking residues, is its ability to act as an amine acceptor in a transglutaminase-catalyzed reaction and to make a glutamyl–lysine cross-link with a neighboring polypeptide. To learn whether glutamine repeats can act as amine acceptors, we have made peptides with variable lengths of polyglutamine flanked by the adjacent amino acid residues in the proteins associated with spinocerebellar ataxia type 1 (SCA1), Machado–Joseph disease (SCA3), or dentato-rubral pallido-luysian atrophy (DRPLA) or those residues adjacent to the preferred cross-linking site of involucrin, or solely by arginine residues. The polyglutamine was found to confer excellent substrate properties on any soluble peptide; under optimal conditions, virtually all the glutamine residues acted as amine acceptors in the reaction with glycine ethyl-ester, and lengthening the sequence of polyglutamine increased the reactivity of each glutamine residue. In the presence of transglutaminase, peptides containing polyglutamine formed insoluble aggregates with the proteins of brain extracts and these aggregates contained glutamyl–lysine cross-links. Repeated glutamine residues exposed on the surface of a neuronal protein should form cross-linked aggregates in the presence of any transglutaminase activated by the presence of Ca2+.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=26176Documentos Relacionados
- Crosslinking and labeling of membrane proteins by transglutaminase-catalyzed reactions.
- Sorting-out of acceptor-donor relationships in the transglutaminase-catalyzed cross-linking of crystallins by the enzyme-directed labeling of potential sites
- Sorting-out of acceptor-donor relationships in the transglutaminase-catalyzed cross-linking of crystallins by the enzyme-directed labeling of potential sites.
- Transglutaminase-catalyzed crosslinking of the Aα and γ constituent chains in fibrinogen
- Transglutaminase-catalyzed reaction is important for molting of Onchocerca volvulus third-stage larvae.
