Fibrillar vs Crystalline Full-Length beta-2-Microglobulin Studied by High-Resolution Solid-State NMR Spectroscopy

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.


Published in:
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 132, 16, 5556+
Year:
2010
Publisher:
AMER CHEMICAL SOC
ISSN:
0002-7863
Laboratories:




 Record created 2015-01-08, last modified 2018-03-17


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