Home > Publications database > Pyroglutamate formation influences solubility and amyloidogenicity of amyloid peptides. A driving force in different neurodegenerative disorders? > print

001     6518
005     20200402205710.0
024 7 _ |2 pmid
|a pmid:19518051
024 7 _ |2 DOI
|a 10.1021/bi900818a
024 7 _ |2 WOS
|a WOS:000268175600035
024 7 _ |a altmetric:21802862
|2 altmetric
037 _ _ |a PreJuSER-6518
041 _ _ |a eng
082 _ _ |a 570
084 _ _ |2 WoS
|a Biochemistry & Molecular Biology
100 1 _ |a Schlenzig, D.
|b 0
|0 P:(DE-HGF)0
245 _ _ |a Pyroglutamate formation influences solubility and amyloidogenicity of amyloid peptides. A driving force in different neurodegenerative disorders?
260 _ _ |a Columbus, Ohio
|b American Chemical Society
|c 2009
300 _ _ |a 7072 - 7078
336 7 _ |a Journal Article
|0 PUB:(DE-HGF)16
|2 PUB:(DE-HGF)
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|0 0
|2 EndNote
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a article
|2 DRIVER
440 _ 0 |a Biochemistry
|x 0006-2960
|0 798
|y 29
|v 48
500 _ _ |a Record converted from VDB: 12.11.2012
520 _ _ |a N-Terminally truncated and pyroglutamate (pGlu) modified amyloid beta (Abeta) peptides are major constituents of amyloid deposits in sporadic and inherited Alzheimer's disease (AD). Formation of pGlu at the N-terminus confers resistance against cleavage by most aminopeptidases, increases toxicity of the peptides, and may seed Abeta aggregate formation. Similarly, the deposited amyloid peptides ABri and ADan, which cause a very similar histopathology in familial British dementia (FBD) and familial Danish dementia (FDD), are N-terminally blocked by pGlu. Triggered by the coincidence of pGlu-modified amyloid peptides and similar pathology in AD, FBD, and FDD, we investigated the impact of N-terminal pGlu on biochemical and biophysical properties of Abeta, ABri, and ADan. N-Terminal pGlu increases the hydrophobicity and changes the pH-dependent solubility profile, rendering the pGlu-modified peptides less soluble in the basic pH range. The pGlu residue increases the aggregation propensity of all amyloid peptides as evidenced by ThT fluorescence assays and dynamic light scattering. The far-UV CD spectroscopic analysis points toward an enhanced beta-sheet structure of the pGlu-Abeta. Importantly, changes in fibril morphology are clearly caused by the N-terminal pGlu, resulting in the formation of short fibers, which are frequently arranged in bundles. The effect of pGlu on the morphology is virtually indistinguishable between ABri, ADan, and Abeta. The data provide evidence for a comparable influence of the pGlu modification on the aggregation process of structurally different amyloid peptides, thus likely contributing to the molecularly distinct neurodegenerative diseases AD, FBD, and FDD. The main driving force for the aggregation is apparently an increase in the hydrophobicity and thus an accelerated seed formation.
536 _ _ |a Funktion und Dysfunktion des Nervensystems
|c P33
|2 G:(DE-HGF)
|0 G:(DE-Juel1)FUEK409
|x 0
588 _ _ |a Dataset connected to Web of Science, Pubmed
650 _ 2 |2 MeSH
|a Alzheimer Disease: metabolism
650 _ 2 |2 MeSH
|a Amino Acid Sequence
650 _ 2 |2 MeSH
|a Amyloid: chemistry
650 _ 2 |2 MeSH
|a Amyloid: metabolism
650 _ 2 |2 MeSH
|a Amyloid: ultrastructure
650 _ 2 |2 MeSH
|a Circular Dichroism
650 _ 2 |2 MeSH
|a Humans
650 _ 2 |2 MeSH
|a Hydrogen-Ion Concentration
650 _ 2 |2 MeSH
|a Microscopy, Electron
650 _ 2 |2 MeSH
|a Molecular Sequence Data
650 _ 2 |2 MeSH
|a Peptides: chemistry
650 _ 2 |2 MeSH
|a Peptides: metabolism
650 _ 2 |2 MeSH
|a Pyrrolidonecarboxylic Acid: metabolism
650 _ 2 |2 MeSH
|a Solubility
650 _ 2 |2 MeSH
|a Spectrophotometry, Ultraviolet
650 _ 7 |0 0
|2 NLM Chemicals
|a Amyloid
650 _ 7 |0 0
|2 NLM Chemicals
|a Peptides
650 _ 7 |0 98-79-3
|2 NLM Chemicals
|a Pyrrolidonecarboxylic Acid
650 _ 7 |a J
|2 WoSType
700 1 _ |a Manhart, S.
|b 1
|0 P:(DE-HGF)0
700 1 _ |a Cinar, Y.
|b 2
|u FZJ
|0 P:(DE-Juel1)VDB88687
700 1 _ |a Willbold, D.
|b 3
|u FZJ
|0 P:(DE-Juel1)132029
700 1 _ |a Funke, S. A.
|b 4
|u FZJ
|0 P:(DE-Juel1)VDB65869
700 1 _ |a Kleinschmidt, M.
|b 5
|0 P:(DE-HGF)0
700 1 _ |a Hause, G.
|b 6
|0 P:(DE-HGF)0
700 1 _ |a Schilling, S.
|b 7
|0 P:(DE-HGF)0
700 1 _ |a Demuth, H.-U.
|b 8
|0 P:(DE-HGF)0
773 _ _ |a 10.1021/bi900818a
|g Vol. 48, p. 7072 - 7078
|p 7072 - 7078
|q 48<7072 - 7078
|0 PERI:(DE-600)1472258-6
|t Biochemistry
|v 48
|y 2009
|x 0006-2960
856 7 _ |u http://dx.doi.org/10.1021/bi900818a
909 C O |o oai:juser.fz-juelich.de:6518
|p VDB
913 1 _ |k P33
|v Funktion und Dysfunktion des Nervensystems
|l Funktion und Dysfunktion des Nervensystems
|b Gesundheit
|0 G:(DE-Juel1)FUEK409
|x 0
914 1 _ |y 2009
915 _ _ |0 StatID:(DE-HGF)0010
|a JCR/ISI refereed
920 1 _ |d 31.12.2010
|g ISB
|k ISB-3
|l Strukturbiochemie
|0 I:(DE-Juel1)VDB942
|x 0
920 1 _ |0 I:(DE-82)080012_20140620
|k JARA-HPC
|l Jülich Aachen Research Alliance - High-Performance Computing
|g JARA
|x 1
970 _ _ |a VDB:(DE-Juel1)114831
980 _ _ |a VDB
980 _ _ |a ConvertedRecord
980 _ _ |a journal
980 _ _ |a I:(DE-Juel1)ICS-6-20110106
980 _ _ |a I:(DE-82)080012_20140620
980 _ _ |a UNRESTRICTED
981 _ _ |a I:(DE-Juel1)IBI-7-20200312
981 _ _ |a I:(DE-Juel1)ICS-6-20110106
981 _ _ |a I:(DE-Juel1)VDB1346

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