Robert Silvers
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View article: Aducanumab binding to Aβ <sub>1-42</sub> fibrils alters dynamics of the N-terminal tail while preserving the fibril core
Aducanumab binding to Aβ <sub>1-42</sub> fibrils alters dynamics of the N-terminal tail while preserving the fibril core Open
Aducanumab, a human IgG1 antibody with plaque-clearing effects and modest clinical benefit, binds selectively to aggregated Aβ via the N-terminal region. Yet, the molecular details of how the antibody engages Aβ 1-42 fibrils remain unresol…
View article: Aducanumab Binding to Aβ1-42 Fibrils Alters Dynamics of the N-Terminal Tail While Preserving the Fibril Core
Aducanumab Binding to Aβ1-42 Fibrils Alters Dynamics of the N-Terminal Tail While Preserving the Fibril Core Open
Aducanumab, a human IgG1 antibody with plaque-clearing effects and modest clinical benefit, binds selectively to aggregated Aβ via the N-terminal region. Yet, the molecular details of how the antibody engages Aβ 1-42 fibrils remain unresol…
View article: Fluorescent Dyes for Differential Scanning Fluorimetry of RNA
Fluorescent Dyes for Differential Scanning Fluorimetry of RNA Open
Differential scanning fluorimetry (DSF) to determine the thermal stability of RNA has only recently been adapted from proteins using the nucleic acid dye RiboGreen. Here, we investigate the suitability of seven commercially available nucle…
View article: Noncanonical RNA binding of human La-related protein 6
Noncanonical RNA binding of human La-related protein 6 Open
La-related proteins (LARPs) are RNA-binding proteins that are involved in a variety of disease-related processes. Most LARPs recognize short single-stranded poly(U/A) motifs via a conserved hydrophobic pocket. Human LARP6 (HsLARP6) is an e…
View article: Non-Canonical RNA Binding of Human La-related Protein 6
Non-Canonical RNA Binding of Human La-related Protein 6 Open
La-related proteins (LARPs) are RNA-binding proteins that are involved in a variety of disease-related processes. Most LARPs recognize short single-stranded poly(U/A) motifs via a conserved hydrophobic pocket. Human LARP6 (HsLARP6) is an e…
View article: A Robust Expression and Purification Protocol for the Production of the La Domain of Human LARP6
A Robust Expression and Purification Protocol for the Production of the La Domain of Human LARP6 Open
Human La-related protein 6 (HsLARP6) regulates the highly organized biosynthesis of type I procollagen polypeptides and affects the proper assembly of procollagen peptides into heterotrimers of type I procollagen. HsLARP6-mediated regulati…
View article: A Robust Expression and Purification Protocol for the Production of the La Domain of Human LARP6
A Robust Expression and Purification Protocol for the Production of the La Domain of Human LARP6 Open
Human La-related protein 6 (HsLARP6) regulates the highly organized biosynthesis of type I procollagen polypeptides and affects proper assembly of procollagen peptides into heterotrimers of type I procollagen. HsLARP6-mediated regulation o…
View article: NMR Resonance Assignment of the LA Motif of Human LA-Related Protein 1
NMR Resonance Assignment of the LA Motif of Human LA-Related Protein 1 Open
Human La-related protein 1 (HsLARP1) is involved in post-transcriptional regulation of certain 5’ s terminal oligopyrimidine (5’TOP) mRNAs as well as other mRNAs and binds to both the 5’TOP motif and the 3’-poly(A) tail of certain mRNAs. H…
View article: <sup>1</sup> H detection and dynamic nuclear polarization–enhanced NMR of Aβ <sub>1-42</sub> fibrils
<sup>1</sup> H detection and dynamic nuclear polarization–enhanced NMR of Aβ <sub>1-42</sub> fibrils Open
Significance Amyloid-β (Aβ) is the subject of intense scrutiny because of its close association with Alzheimer’s disease (AD), which currently afflicts about 50 million people worldwide. The results reported in this manuscript focus on the…
View article: Molecular Basis of Ca(II)-Induced Tetramerization and Transition-Metal Sequestration in Human Calprotectin
Molecular Basis of Ca(II)-Induced Tetramerization and Transition-Metal Sequestration in Human Calprotectin Open
Human calprotectin (CP, S100A8/S100A9 oligomer, MRP8/MRP14 oligomer) is an abundant innate immune protein that contributes to the host metal-withholding response. Its ability to sequester transition metal nutrients from microbial pathogens…
View article: Characterization of sequence specific binding of LARP6 to the 5’ stem-loop of type I collagen mRNAs and implications for rational design of antifibrotic drugs
Characterization of sequence specific binding of LARP6 to the 5’ stem-loop of type I collagen mRNAs and implications for rational design of antifibrotic drugs Open
Excessive synthesis of type I collagen characterizes fibrotic diseases. Binding of LARP6 to the 5’ stem-loop (5’SL) of collagen mRNAs regulates their translation and the high rate of biosynthesis in fibrosis. LARP6 needs two domains to for…
View article: The structure of a β2-microglobulin fibril suggests a molecular basis for its amyloid polymorphism
The structure of a β2-microglobulin fibril suggests a molecular basis for its amyloid polymorphism Open
All amyloid fibrils contain a cross-β fold. How this structure differs in fibrils formed from proteins associated with different diseases remains unclear. Here, we combine cryo-EM and MAS-NMR to determine the structure of an amyloid fibril…
View article: Cover Feature: Impact of Azidohomoalanine Incorporation on Protein Structure and Ligand Binding (ChemBioChem 23/2017)
Cover Feature: Impact of Azidohomoalanine Incorporation on Protein Structure and Ligand Binding (ChemBioChem 23/2017) Open
The cover feature picture shows the structure of the unnatural amino acid–modified PDZ3 domain, which was thoroughly investigated by NMR spectroscopy and X-ray crystallography. Azidohomoalanine was introduced by expression in methionine au…
View article: Proton-Assisted Recoupling (PAR) in Peptides and Proteins
Proton-Assisted Recoupling (PAR) in Peptides and Proteins Open
Proton-assisted recoupling (PAR) is examined by exploring optimal experimental conditions and magnetization transfer rates in a variety of biologically relevant nuclear spin-systems, including simple amino acids, model peptides, and two pr…
View article: Impact of Azidohomoalanine Incorporation on Protein Structure and Ligand Binding
Impact of Azidohomoalanine Incorporation on Protein Structure and Ligand Binding Open
The impact of the incorporation of a non‐natural amino acid (NNAA) on protein structure, dynamics, and ligand binding has not been studied rigorously so far. NNAAs are regularly used to modify proteins post‐translationally in vivo and in v…
View article: Aggregation and Fibril Structure of Aβ<sub>M01–42</sub> and Aβ<sub>1–42</sub>
Aggregation and Fibril Structure of Aβ<sub>M01–42</sub> and Aβ<sub>1–42</sub> Open
A mechanistic understanding of Aβ aggregation and high-resolution structures of Aβ fibrils and oligomers are vital to elucidating relevant details of neurodegeneration in Alzheimer's disease, which will facilitate the rational design of di…
View article: 3D MAS NMR Experiment Utilizing Through-Space
3D MAS NMR Experiment Utilizing Through-Space Open
We demonstrate a novel 3D NNC magic angle spinning NMR experiment that generates ¹⁵N–¹⁵N internuclear contacts in protein systems using an optimized ¹⁵N–¹⁵N proton assisted recoupling (PAR) mixing period and a ¹³C dimension for improved re…
View article: 3D MAS NMR Experiment Utilizing Through-Space <sup>15</sup>N–<sup>15</sup>N Correlations
3D MAS NMR Experiment Utilizing Through-Space <sup>15</sup>N–<sup>15</sup>N Correlations Open
We demonstrate a novel 3D NNC magic angle spinning NMR experiment that generates 15N-15N internuclear contacts in protein systems using an optimized 15N-15N proton assisted recoupling (PAR) mixing period and a 13C dimension for improved re…
View article: Lipid-Bilayer-Bound Conformation of an Integral Membrane beta-Barrel Protein by Multidimensional MAS NMR
Lipid-Bilayer-Bound Conformation of an Integral Membrane beta-Barrel Protein by Multidimensional MAS NMR Open
The human voltage dependent anion channel 1 (VDAC) is a 32 kDa β-barrel integral membrane protein that controls the transport of ions across the outer mitochondrial membrane. Despite the determination of VDAC solution and diffraction struc…
View article: Gd(III) and Mn(II) complexes for dynamic nuclear polarization: small molecular chelate polarizing agents and applications with site-directed spin labeling of proteins
Gd(III) and Mn(II) complexes for dynamic nuclear polarization: small molecular chelate polarizing agents and applications with site-directed spin labeling of proteins Open
We investigate complexes of two paramagnetic metal ions Gd³⁺ and Mn²⁺ to serve as polarizing agents for solid-state dynamic nuclear polarization (DNP) of ¹H, ¹³C, and ¹⁵N at magnetic fields of 5, 9.4, and 14.1 T. Both ions are half-integer…
View article: Atomic Resolution Structure of Monomorphic Aβ<sub>42</sub> Amyloid Fibrils
Atomic Resolution Structure of Monomorphic Aβ<sub>42</sub> Amyloid Fibrils Open
Amyloid-β (Aβ) is a 39-42 residue protein produced by the cleavage of the amyloid precursor protein (APP), which subsequently aggregates to form cross-β amyloid fibrils that are a hallmark of Alzheimer's disease (AD). The most prominent fo…
View article: Gd(<scp>iii</scp>) and Mn(<scp>ii</scp>) complexes for dynamic nuclear polarization: small molecular chelate polarizing agents and applications with site-directed spin labeling of proteins
Gd(<span>iii</span>) and Mn(<span>ii</span>) complexes for dynamic nuclear polarization: small molecular chelate polarizing agents and applications with site-directed spin labeling of proteins Open
Metal complexes based on Gd(iii) and Mn(ii) spin-labels can be utilized for dynamic nuclear polarization of 1H, 13C, and 15N.