title: Di-tyrosine cross-link decreases the collisional cross-section of aβ peptide dimers and trimers in the gas phase: an ion mobility study.
abstract: Oligomeric forms of Aβ peptide are most likely the main synaptotoxic and neurotoxic agent in Alzheimer's disease. Toxicity of various Aβ oligomeric forms has been confirmed in vivo and also in vitro. However, in vitro preparations were found to be orders of magnitude less toxic than oligomers obtained from in vivo sources. This difference can be explained by the presence of a covalent cross-link, which would stabilize the oligomer. In the present work, we have characterized the structural properties of Aβ dimers and trimers stabilized by di- and tri-tyrosine cross-links. Using ion mobility mass spectrometry we have compared the collisional cross-section of non-cross-linked and cross-linked species. We have found that the presence of cross-links does not generate new unique forms but rather shifts the equilibrium towards more compact oligomer types that can also be detected for non-cross-linked peptide. In consequence, more extended forms, probable precursors of off-pathway oligomeric species, become relatively destabilized in cross-linked oligomers and the pathway of oligomer evolution becomes redirected towards fibrillar structures.
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Science, Warszawa, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sitkiewicz
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Science, Warszawa, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Olędzki
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Science, Warszawa, Poland.
authors.forename: Jarosław
authors.initials: J
authors.lastname: Poznański
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Science, Warszawa, Poland; Institute of Genetics and Biotechnology, Biology Department, Warsaw University, Warszawa, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Dadlez
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D005740:Gases / Q000737:chemistry*; D007477:Ions; D013058:Mass Spectrometry; D008958:Models, Molecular; D008970:Molecular Weight; D055503:Protein Multimerization; D013050:Spectrometry, Fluorescence; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D003432:Cross-Linking Reagents; D005740:Gases; D007477:Ions; D014443:Tyrosine; C007543:dityrosine