Research Data Leeds Repository

Structural mapping of oligomeric intermediates in an amyloid assembly pathway - dataset

Karamanos, Theodoros and Jackson, Matthew P and Calabrese, Antonio N and Goodchild, Sophia C and Cawood, Emma E and Thompson, Gary S and Kalverda, Arnout P and Hewitt, Eric W and Radford, Sheena (2019) Structural mapping of oligomeric intermediates in an amyloid assembly pathway - dataset. University of Leeds. [Dataset] https://doi.org/10.5518/329

Dataset description

Transiently populated oligomers are commonly formed in the early stages of amyloid assembly. Determining the structure(s) of these species and defining their role(s) in assembly are key to developing routes to prevent or delay disease. Here, using a combination of chemical kinetics, NMR spectroscopy, native mass spectrometry and other biophysical methods, we identify and structurally characterise the oligomers required for amyloid assembly of the naturally occurring variant of β2-microglobulin, DN6. The results reveal a remarkably specific assembly pathway involving the formation hexamers that are non-toxic and retain a native-like immunoglobulin fold, but in which the C-terminal strand is unfurled ready to initiate the transition into the amyloid fold. The results suggest new avenues to combat disease by specific targeting of the early intermediates in amyloid assembly.

Additional information:	These data are associated with a paper accepted for publication. Any updates to the data will be recorded and dated.
Subjects:	C000 - Biological sciences > C700 - Molecular biology, biophysics & biochemistry
Divisions:	Faculty of Biological Sciences > School of Molecular and Cellular Biology
Related resources:	Location Type http://eprints.whiterose.ac.uk/151478/ Publication https://doi.org/10.7554/elife.46574 Publication
License:	Creative Commons Attribution 4.0 International (CC BY 4.0)
Date deposited:	04 Oct 2019 11:42
URI:	http://archive.researchdata.leeds.ac.uk/id/eprint/579
Additional details Additional details Creators: Creators ORCID Other ID Email Primary affiliation Primary affiliation ID Primary affiliation ID type Secondary affiliation Secondary affiliation ID Secondary affiliation ID type Karamanos, Theodoros https://orcid.org/0000-0003-2297-540X University of Leeds https://doi.org/10.13039/501100000777 Crossref Jackson, Matthew P https://orcid.org/0000-0002-4416-3499 University of Leeds https://doi.org/10.13039/501100000777 Crossref Calabrese, Antonio N https://orcid.org/0000-0003-2437-7761 University of Leeds https://doi.org/10.13039/501100000777 Crossref Goodchild, Sophia C University of Leeds https://doi.org/10.13039/501100000777 Crossref Cawood, Emma E https://orcid.org/0000-0002-2707-8022 University of Leeds https://doi.org/10.13039/501100000777 Crossref Thompson, Gary S University of Leeds https://doi.org/10.13039/501100000777 Crossref Kalverda, Arnout P University of Leeds https://doi.org/10.13039/501100000777 Crossref Hewitt, Eric W https://orcid.org/0000-0002-6238-6303 University of Leeds https://doi.org/10.13039/501100000777 Crossref Radford, Sheena https://orcid.org/0000-0002-3079-8039 University of Leeds https://doi.org/10.13039/501100000777 Crossref Type of data: Dataset Research funders: Wellcome Trust, European Research Council Grant numbers: 089311/Z/09/Z, 109154/Z/15/Z, 204963, 322408 Publication date: 2019 Resource language: English Metadata language: English Publisher: University of Leeds Contact Email Address: S.E.Radford@leeds.ac.uk Last Modified: 10 Jun 2020 17:12

Files

Documentation

Readme [601B] Readme [601B] Readme [601B] Visible to: Anyone File name: readme.txt Content type: Documentation Mime-Type: text/plain License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 601B

Data

Structural model of DN6 hexamers [766kB] Structural model of DN6 hexamers [766kB] Structural model of DN6 hexamers [766kB] Visible to: Anyone File name: refineDN6Hexamer_withNOE_wat_0_chainID.pdb Content type: Data Description: Lowest energy hexamer model (PDB file) Mime-Type: application/vnd.palm License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 766kB

Structural model of DN6 dimers [245kB] Structural model of DN6 dimers [245kB] Structural model of DN6 dimers [245kB] Visible to: Anyone File name: refDN6dimer_with4PRE_wat_0.pdb Content type: Data Description: Lowest energy dimer model (PDB file) Mime-Type: application/vnd.palm License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 245kB

Alternative dimer model [291kB] Alternative dimer model [291kB] Alternative dimer model [291kB] Visible to: Anyone File name: calcDN6dimer_with4PRE_dSYMM_Vgyr_80.pdb Content type: Data Description: The second/higher enrgy DN6 dimer (PDB file) Mime-Type: application/vnd.palm License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 291kB

HN PRE data for position 20 [2kB] HN PRE data for position 20 [2kB] HN PRE data for position 20 [2kB] Visible to: Anyone File name: PRE_S20_fit_47.txt Content type: Data Description: residue, calculated PRE from dimer A, measured PRE, error (1H relaxation rates (per s)) Mime-Type: text/plain License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 2kB

HN PRE data for position 33 [2kB] HN PRE data for position 33 [2kB] HN PRE data for position 33 [2kB] Visible to: Anyone File name: PRE_S33_fit_47.txt Content type: Data Description: residue, calculated PRE rfom dimer A, measured PRE, error (1H relaxation rates (per s)) Mime-Type: text/plain License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 2kB

HN PRE data for position 54 [2kB] HN PRE data for position 54 [2kB] HN PRE data for position 54 [2kB] Visible to: Anyone File name: PRE_L54_fit_47.txt Content type: Data Description: residue, calculated PRE from dimer A, measured PRE, error (1H relaxation rates (per s)) Mime-Type: text/plain License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 2kB

HN PRE data for position 61 [2kB] HN PRE data for position 61 [2kB] HN PRE data for position 61 [2kB] Visible to: Anyone File name: PRE_S61_fit_47.txt Content type: Data Description: residue, calculated PRE from dimer A, measured PRE, error (1H relaxation rates (per s)) Mime-Type: text/plain License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 2kB

ΔΝ6 seeding [6kB] ΔΝ6 seeding [6kB] ΔΝ6 seeding [6kB] Visible to: Anyone File name: DN6_20uM_seeds_averages.txt Content type: Data Description: Average trace (from 5 replicates) for DN6 seeding at different concentrations (ThT fluoresnce data) Mime-Type: text/plain License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 6kB

HSQC spectrum of ΔΝ6 [2MB] HSQC spectrum of ΔΝ6 [2MB] HSQC spectrum of ΔΝ6 [2MB] Visible to: Anyone File name: 10uM_DN6.ft2 Content type: Data Description: 10uM (2D NMR spectrum) License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 2MB

HSQC spectrum of ΔΝ6 [2MB] HSQC spectrum of ΔΝ6 [2MB] HSQC spectrum of ΔΝ6 [2MB] Visible to: Anyone File name: 500uM_DN6.ft2 Content type: Data Description: 500uM (2D NMR spectrum) License: Creative Commons Attribution 4.0 International (CC BY 4.0) File size: 2MB