[NMR paper] Effect of amino acid mutations on the conformational dynamics of amyloidogenic immunoglobulin light-chains: A combined NMR and in silico study.
Related ArticlesEffect of amino acid mutations on the conformational dynamics of amyloidogenic immunoglobulin light-chains: A combined NMR and in silico study.
Abstract
The conformational dynamics of a pathogenic ?4 human immunoglobulin light-chain variable domain, SMA, associated with AL amyloidosis, were investigated by (15)N relaxation dispersion NMR spectroscopy. Compared to a homologous light-chain, LEN, which differs from SMA at eight positions but is non-amyloidogenic in vivo, we find that multiple residues in SMA clustered around the N-terminus and CDR loops experience considerable conformational exchange broadening caused by millisecond timescale protein motions, consistent with a destabilized dimer interface. To evaluate the contribution of each amino acid substitution to shaping the dynamic conformational landscape of SMA, NMR studies were performed for each SMA-like point mutant of LEN followed by in silico analysis for a subset of these proteins. These studies show that a combination of only three mutations located within or directly adjacent to CDR3 loop at the dimer interface, which remarkably include both destabilizing (Q89H and Y96Q) and stabilizing (T94H) mutations, largely accounts for the differences in conformational flexibility between LEN and SMA. Collectively, our studies indicate that a correct combination of stabilizing and destabilizing mutations is key for immunoglobulin light-chains populating unfolded intermediates that result in amyloid formation, and underscore the complex nature of correlations between light-chain conformational flexibility, thermodynamic stability and amyloidogenicity.
[NMR paper] The nearest-neighbor effect on random-coil NMR chemical shifts demonstrated using a low-complexity amino-acid sequence.
The nearest-neighbor effect on random-coil NMR chemical shifts demonstrated using a low-complexity amino-acid sequence.
Related Articles The nearest-neighbor effect on random-coil NMR chemical shifts demonstrated using a low-complexity amino-acid sequence.
Protein Pept Lett. 2016 Sep 20;
Authors: Chen TC, Hsiao CL, Huang SJ, Huang JR
Abstract
In NMR experiments, the chemical shift is typically the first parameter measured and is a source of structural information for biomolecules. Indeed, secondary chemical shifts, the difference...
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09-23-2016 12:55 PM
[NMR paper] Cell-free expression of the APP transmembrane fragments with Alzheimer's disease mutations using algal amino acid mixture for structural NMR studies.
Cell-free expression of the APP transmembrane fragments with Alzheimer's disease mutations using algal amino acid mixture for structural NMR studies.
Related Articles Cell-free expression of the APP transmembrane fragments with Alzheimer's disease mutations using algal amino acid mixture for structural NMR studies.
Protein Expr Purif. 2016 Apr 9;
Authors: Bocharova OV, Urban AS, Nadezhdin KD, Bocharov EV, Arseniev AS
Abstract
Structural investigations need ready supply of the isotope labeled proteins with inserted mutations n the...
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04-14-2016 12:01 PM
Paramagnetic relaxation enhancement of membrane proteins by incorporation of the metal-chelating unnatural amino acid 2-amino-3-(8-hydroxyquinolin-3-yl)propanoic acid (HQA)
Paramagnetic relaxation enhancement of membrane proteins by incorporation of the metal-chelating unnatural amino acid 2-amino-3-(8-hydroxyquinolin-3-yl)propanoic acid (HQA)
Abstract
The use of paramagnetic constraints in protein NMR is an active area of research because of the benefits of long-range distance measurements (>10Â*Ã?). One of the main issues in successful execution is the incorporation of a paramagnetic metal ion into diamagnetic proteins. The most common metal ion tags are relatively long aliphatic chains attached to the side chain of a...
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[NMR paper] NMR conformational dynamics of an Anthrax Lethal Factor domain studied by multiple amino acid-selective labeling.
NMR conformational dynamics of an Anthrax Lethal Factor domain studied by multiple amino acid-selective labeling.
Related Articles NMR conformational dynamics of an Anthrax Lethal Factor domain studied by multiple amino acid-selective labeling.
Biochem Biophys Res Commun. 2014 Jun 2;
Authors: Vourtsis DJ, Chasapis CT, Pairas G, Bentrop D, Spyroulias GA
Abstract
NMR-based structural biology urgently needs cost- and time-effective methods to assist both in the process of acquiring high-resolution NMR spectra and their subsequent...
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06-20-2014 08:14 PM
[NMR paper] The Involvement of Amino Acid Side Chains in Shielding the Nickel Coordination Site: An NMR Study.
The Involvement of Amino Acid Side Chains in Shielding the Nickel Coordination Site: An NMR Study.
The Involvement of Amino Acid Side Chains in Shielding the Nickel Coordination Site: An NMR Study.
Molecules. 2013;18(10):12396-12414
Authors: Medici S, Peana M, Nurchi VM, Zoroddu MA
Abstract
Coordination of proteins and peptides to metal ions is known to affect their properties, often by a change in their structural organization. Side chains of the residues directly involved in metal binding or very close to the coordination centre...
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[NMR paper] Solid-state NMR study reveals Collagen I structural modifications of amino-acid side chains upon fibrillogenesis.
Solid-state NMR study reveals Collagen I structural modifications of amino-acid side chains upon fibrillogenesis.
Related Articles Solid-state NMR study reveals Collagen I structural modifications of amino-acid side chains upon fibrillogenesis.
J Biol Chem. 2013 Jan 22;
Authors: De Sa Peixoto P, Laurent G, Azais T, Mosser G
Abstract
In vivo, collagen I, the major structural protein in human body, is found assembled into fibrils. In the present work, we study a high concentrated collagen sample in its soluble, fibrillar and denatured states...
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02-03-2013 10:19 AM
4D APSY-HBCB(CG)CDHD experiment for automated assignment of aromatic amino acid side chains in proteins
4D APSY-HBCB(CG)CDHD experiment for automated assignment of aromatic amino acid side chains in proteins
Abstract A four-dimensional (4D) APSY (automated projection spectroscopy)-HBCB(CG)CDHD experiment is presented. This 4D experiment correlates aromatic with aliphatic carbon and proton resonances from the same amino acid side chain of proteins in aqueous solution. It thus allows unambiguous sequence-specific assignment of aromatic amino acid ring signals based on backbone assignments. Compared to conventional 2D approaches, the inclusion of evolution periods on 1Hβ and 13Cδ...
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[NMR paper] Dynamics of the carbohydrate chains attached to the Fc portion of immunoglobulin G as
Dynamics of the carbohydrate chains attached to the Fc portion of immunoglobulin G as studied by NMR spectroscopy assisted by selective 13C labeling of the glycans.
Related Articles Dynamics of the carbohydrate chains attached to the Fc portion of immunoglobulin G as studied by NMR spectroscopy assisted by selective 13C labeling of the glycans.
J Biomol NMR. 1998 Oct;12(3):385-94
Authors: Yamaguchi Y, Kato K, Shindo M, Aoki S, Furusho K, Koga K, Takahashi N, Arata Y, Shimada I
A systematic method for 13C labeling of the glycan of...
Effect of amino acid mutations on the conformational dynamics of amyloidogenic immunoglobulin light-chains: A combined NMR and in silico study.
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