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Data for Metal ion binding to the amyloid beta monomer studied by native top-down FTICR mass spectrometry
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Lermyte, Frederik, Everett, James, Lam, Yuko P. Y., Wootton, Christopher, Brooks, Jake, Barrow, Mark P., Telling, Neil D., Sadler, P. J., O'Connor, Peter B. and Collingwood, Joanna F. (2019) Data for Metal ion binding to the amyloid beta monomer studied by native top-down FTICR mass spectrometry. [Dataset]
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Readme.txt - Supplemental Material Available under License Creative Commons Attribution 4.0. Download (626b) |
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Data Lermyte_JASMS_2019.zip - Published Version Available under License Creative Commons Attribution 4.0. Download (1355Mb) |
Official URL: http://wrap.warwick.ac.uk/122328
Abstract
Native top-down mass spectrometry is a fast, robust biophysical technique that can provide molecular-scale information on the interaction between proteins or peptides and ligands, including metal cations. Here we have analyzed complexes of the full-length amyloid β (1-42) monomer with a range of (patho)physiologically relevant metal cations using native Fourier transform ion cyclotron resonance mass spectrometry and three different fragmentation methods—collision-induced dissociation, electron capture dissociation, and infrared multiphoton dissociation—all yielding consistent results. Amyloid β is of particular interest as its oligomerization and aggregation are major events in the etiology of Alzheimer’s disease, and it is known that interactions between the peptide and bioavailable metal cations have the potential to significantly damage neurons. Those metals which exhibited the strongest binding to the peptide (Cu2+, Co2+, Ni2+) all shared a very similar binding region containing two of the histidine residues near the N-terminus (His6, His13). Notably, Fe3+ bound to the peptide only when stabilized toward hydrolysis, aggregation, and precipitation by a chelating ligand, binding in the region between Ser8 and Gly25. We also identified two additional binding regions near the flexible, hydrophobic C-terminus, where other metals (Mg2+, Ca2+, Mn2+, Na+, and K+) bound more weakly—one centered on Leu34, and one on Gly38. Unexpectedly, collisional activation of the complex formed between the peptide and [CoIII(NH3)6]3+ induced gas-phase reduction of the metal to CoII, allowing the peptide to fragment via radical-based dissociation pathways. This work demonstrates how native mass spectrometry can provide new insights into the interactions between amyloid β and metal cations.
| Item Type: | Dataset | |||||||||
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| Subjects: | Q Science > QD Chemistry Q Science > QP Physiology T Technology > TA Engineering (General). Civil engineering (General) |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Engineering > Engineering |
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| Type of Data: | Experimental data | |||||||||
| Library of Congress Subject Headings (LCSH): | Metalloproteins -- Analysis, Proteomics, Mass spectrometry, Proteins -- Analysis, Peptides -- Analysis, Nuclear magnetic resonance spectroscopy | |||||||||
| Publisher: | University of Warwick, School of Engineering | |||||||||
| Official Date: | 9 September 2019 | |||||||||
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| Status: | Not Peer Reviewed | |||||||||
| Publication Status: | Published | |||||||||
| Media of Output (format): | .txt, .ms1, .ms2 | |||||||||
| Access rights to Published version: | Open Access (Creative Commons) | |||||||||
| Copyright Holders: | University of Warwick | |||||||||
| Description: | All 30 FTICR mass spectra are provided as human-readable .ms1 or .ms2 files. File names are composed of Ab(eta)_[attached metal]_[fragmentation technique]. Spectra are provided without any processing (including internal recalibration) other than conversion of Bruker .raw files to non-proprietary format. Data were acquired using a 12T Bruker solariX instrument. Full experimental details can be found in the related paper. |
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| Date of first compliant deposit: | 9 September 2019 | |||||||||
| Date of first compliant Open Access: | 9 September 2019 | |||||||||
| RIOXX Funder/Project Grant: |
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