1H, 13C and 15N resonance assignment of 6aJL2(R25G), a highly fibrillogenic λVI light chain variable domain

Gutiérrez‐González, Luis H.; Muresanu, Lucia; Pozo‐Yauner, Luis del; Sánchez, Rosalba; Güereca, Leopoldo; Becerril, Baltazar; Lücke, Christian

doi:10.1007/s12104-007-9045-9

Cited by 4 publications

(1 citation statement)

References 8 publications

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“…The model protein 6aJL2, a recombinant (r) V L protein within the λ6 subgroup, has a particularly amyloidogenic mutant 6aJL2‐R24G (one should note that here we use continuous numbering of the amino‐acid residues along the protein; an alternative numbering scheme in which Gly24 becomes Gly25 exists). Both proteins have been comprehensively characterized by in vitro fibrillization, and their monomer structures have been determined by X‐ray crystallography and solution‐state NMR .…”

Section: Figurementioning

confidence: 99%

A Substantial Structural Conversion of the Native Monomer Leads to in‐Register Parallel Amyloid Fibril Formation in Light‐Chain Amyloidosis

et al. 2019

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Amyloid light‐chain (AL) amyloidosis is a rare disease in which plasma‐cell‐produced monoclonal immunoglobulin light chains misfold and become deposited as fibrils in the extracellular matrix. λ6 subgroup light chains are particularly fibrillogenic, and around 25 % of amyloid‐associated λ6 light chains exist as the allotypic G24R variant that renders the protein less stable. The molecular details of this process, as well as the structures of the fibrils, are unknown. We have used solid‐state NMR to investigate different fibril polymorphs. The secondary structures derived from NMR predominantly show β‐strands, including in former turn or helical regions, and provide a molecular basis for previously identified fibrillogenic hotspots. We have determined, by using differentially 15N:13C‐labeled samples, that the β‐strands are stacked in‐register parallel in the fibrils. This supramolecular arrangement shows that the native globular folds rearrange substantially upon fibrillization, and rules out the previously hypothesized fibril formation from native monomers.

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Section: Figurementioning

confidence: 99%

A Substantial Structural Conversion of the Native Monomer Leads to in‐Register Parallel Amyloid Fibril Formation in Light‐Chain Amyloidosis

et al. 2019

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Backbone and side-chain 1H, 13C and 15N resonance assignments of LEN, a human immunoglobulin κIV light-chain variable domain

et al. 2009

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(1)H, (13)C and (15)N resonance assignments are presented for a recombinant 114 amino acid human immunoglobulin (Ig) kappaIV light-chain variable domain (VL) LEN, which displays a high degree of sequence identity with another human Ig kappaIV VL, SMA. While SMA is highly amyloidogenic in vivo and in vitro and has been linked to the pathogenesis of light-chain amyloidosis, LEN is non-amyloidogenic in vivo and can be converted to the amyloid state only in vitro under destabilizing conditions. Measurements of longitudinal and transverse amide (15)N relaxation rates confirm that, as expected, LEN is a dimer at physiological pH and typical concentrations used for NMR studies, and the analysis of secondary chemical shifts indicates that the protein has a high beta-sheet content. These findings are consistent with previously published biophysical data and the high-resolution X-ray structure of LEN.

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Solution structure of 6aJL2 and 6aJL2-R24G amyloidogenics light chain proteins

Maya-Martinez

Gil-Rodríguez

Amero

2015

Biochemical and Biophysical Research Communications

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1H, 13C and 15N resonance assignment of 6aJL2(R25G), a highly fibrillogenic λVI light chain variable domain

Cited by 4 publications

References 8 publications

A Substantial Structural Conversion of the Native Monomer Leads to in‐Register Parallel Amyloid Fibril Formation in Light‐Chain Amyloidosis

A Substantial Structural Conversion of the Native Monomer Leads to in‐Register Parallel Amyloid Fibril Formation in Light‐Chain Amyloidosis

Backbone and side-chain 1H, 13C and 15N resonance assignments of LEN, a human immunoglobulin κIV light-chain variable domain

Solution structure of 6aJL2 and 6aJL2-R24G amyloidogenics light chain proteins

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