Fibrillar vs crystalline full-length β-2-microglobulin studied by high-resolution solid-state NMR spectroscopy
Barbet-Massin, Emeline, Ricagno, Stefano, Lewandowski, Józef R., Giorgetti, Sofia, Bellotti, Vittorio, Bolognesi, Martino, Emsley, Lyndon and Pintacuda, Guido. (2010) Fibrillar vs crystalline full-length β-2-microglobulin studied by high-resolution solid-state NMR spectroscopy. Journal of the American Chemical Society, Vol.132 (No.16). pp. 5556-5557. ISSN 0002-7863Full text not available from this repository.
Official URL: http://dx.doi.org/10.1021/ja1002839
Elucidating the fine structure of amyloid fibrils as well as understanding their processes of nucleation and growth remains a difficult yet essential challenge, directly linked to our current poor insight into protein misfolding and aggregation diseases. Here we consider beta-2-microglobulin (beta 2m), the MHC-1 light chain component responsible for dialysis-related amyloidosis, which can give rise to amyloid fibrils in vitro under various experimental conditions, including low and neutral pH. We have used solid-state NMR to probe the structural features of fibrils formed by full-length beta 2m (99 residues) at pH 2.5 and pH 7.4. A close comparison of 2D (13)C-(13)C and (15)N-(13)C correlation experiments performed on beta 2m, in both the crystalline and fibrillar states, suggests that, in spite of structural changes affecting the protein loops linking the protein B-strands, the protein chain retains a substantial share of its native secondary structure in the fibril assembly. Moreover, variations in the chemical shifts of the key Pro32 residue suggest the involvement of a cis-trans isomerization in the process of beta 2m fibril formation. Lastly, the analogy of the spectra recorded on beta 2m fibrils grown at different pH values hints at a conserved architecture of the amyloid species thus obtained.
|Item Type:||Journal Article|
|Subjects:||Q Science > QD Chemistry
Q Science > QP Physiology
|Divisions:||Faculty of Science > Chemistry|
|Library of Congress Subject Headings (LCSH):||Amyloid -- Structure, Nuclear magnetic resonance spectroscopy, Solid state chemistry, Globulins|
|Journal or Publication Title:||Journal of the American Chemical Society|
|Publisher:||American Chemical Society|
|Official Date:||28 April 2010|
|Page Range:||pp. 5556-5557|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||France. Agence nationale de la recherche (ANR), Fondazione Cassa di risparmio delle provincie lombarde, Sixth Framework Programme (European Commission) (FP6), European Union (EU)|
|Grant number:||ANR 08-BLAN-0035-01 (ANR), 2007-5151 (FC), RII3-026145 (FP6), PIRG03-GA-2008-231026 (EU)|
(1) Merlini, G.; Bellotti, V. N. Engl. J. Med. 2003, 349, 583–96.
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