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Structural characterization of transglutaminase-catalyzed cross-linking between glyceraldehyde 3-phosphate dehydrogenase and polyglutamine repeats
- Source :
- Protein Science. 12:170-179
- Publication Year :
- 2003
- Publisher :
- Wiley, 2003.
-
Abstract
- The accumulation of abnormal polyglutamine-containing protein aggregates within the cytosol and nuclei of affected neurons is a hallmark of the progressive neurodegenerative disorders caused by an elongated (CAG)(n) repeat in the genome. The polyglutamine domains are excellent substrates for the enzyme transglutaminase type 2 (tissue), resulting in the formation of cross-links with polypeptides containing lysyl groups. Enzymatic activity toward the Q(n) domains increases greatly upon lengthening of such Q(n) stretches (n40). Among the possible amine donors, the glycolytic enzyme glyceraldehyde-3-phosphate-dehydrogenase was shown to tightly bind several proteins involved in polyglutamine expansion diseases. Recently, the authors have shown that K191, K268, and K331, out of the 26 lysines present in glyceraldehyde-3-phosphate-dehydrogenase, are the reactive amine-donor sites forming cross-links with substance P, which bears the simplest Q(n) domain (n = 2). The present study reports that synthetic peptides of both pathological and nonpathological length (n = 43 and 17, respectively) form cross-links with the same K residues located in the C-terminal region of glyceraldehyde-3-phosphate-dehydrogenase. In addition, it is shown that extra K residues present in the C termini of glyceraldehyde-3-phosphate-dehydrogenase are susceptible to cross-linking in the presence of transglutaminase. The present results indicate a possible modulating effect of Q(n) stretches on tissue transglutaminase substrate specificity and mechanism of recognition.
- Subjects :
- Tissue transglutaminase
Guinea Pigs
Lysine
Protein aggregation
Biochemistry
Article
Catalysis
Substrate Specificity
GTP-binding protein regulators
Trinucleotide Repeats
GTP-Binding Proteins
Animals
Protein Glutamine gamma Glutamyltransferase 2
Glycolysis
Molecular Biology
Glyceraldehyde 3-phosphate dehydrogenase
chemistry.chemical_classification
Transglutaminases
biology
Chemistry
Glyceraldehyde-3-Phosphate Dehydrogenases
Neurodegenerative Diseases
Cytosol
Enzyme
Liver
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
biology.protein
Rabbits
Peptides
Subjects
Details
- ISSN :
- 1469896X and 09618368
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Protein Science
- Accession number :
- edsair.doi.dedup.....7923645219d30b4ac4bf44dedbab34bd