The antibody light chain (LC) consists of two domains and is essential for antigen binding in mature immunoglobulins. The two domains are connected by a highly conserved linker that comprises the structurally important Arg108 residue. In antibody light chain (AL) amyloidosis, a severe protein amyloid disease, the LC and its N-terminal variable domain (V_L) convert ...

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Despite their importance for antibody architecture and design, the principles governing antibody domain stability are still not understood in sufficient detail. Here, to address this question, we chose a domain from the invariant part of IgG, the C_H2 domain. We found that compared with other Ig domains, the isolated C_H2 domain is a surprisingly unstable monomer, ...

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Constitutive NF-κB signaling represents a hallmark of chronic inflammation and autoimmune diseases. The E3 ligase TNF receptor-associated factor 6 (TRAF6) acts as a key regulator bridging innate immunity, pro-inflammatory cytokines, and antigen receptors to the canonical NF-κB pathway. Structural analysis and point mutations have unraveled the essential role of ...

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Post-transcriptional mechanisms play a predominant role in the control of microRNA (miRNA) production. Recognition of the terminal loop of precursor miRNAs by RNA-binding proteins (RBPs) influences their processing; however, the mechanistic basis for how levels of individual or subsets of miRNAs are regulated is mostly unexplored. We previously showed that hnRNP ...

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Solid-state nuclear magnetic resonance (ssNMR) is a spectroscopic technique that is used for characterization of molecular properties in the solid phase at atomic resolution. In particular, using the approach of magic-angle spinning (MAS), ssNMR has seen widespread applications for topics ranging from material sciences to catalysis, metabolomics, and structural ...

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Heat shock protein 90 (Hsp90) is a dimeric molecular chaperone that undergoes large conformational changes during its functional cycle. It has been established that conformational switch points exist in the N-terminal (Hsp90-N) and C-terminal (Hsp90-C) domains of Hsp90, however information for switch points in the large middle-domain (Hsp90-M) is scarce. Here we ...

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Das RGD‐erkennende Integrin αvβ6 trat in jüngster Zeit als vielbeachtete Zielstruktur für die Diagnostik und Therapie von Krebserkrankungen in Erscheinung. Infolgedessen besteht derzeit ein dringender Bedarf an niedermolekularen Liganden für diesen Rezeptor. Ein auf Metadynamik beruhender Ansatz ermöglichte die erfolgreiche Konvertierung eines helikalen ...

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Heat shock protein 90 (Hsp90) is a dimeric molecular chaperone that undergoes large conformational changes during its functional cycle. It has been established that conformational switch points exist in the N-terminal (Hsp90-N) and C-terminal (Hsp90-C) domains of Hsp90, however information for switch points in the large middle-domain (Hsp90-M) is scarce. Here we ...

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In the eukaryotic nucleus, DNA is packaged in the form of nucleosomes, each of which comprises about 147 base pairs of DNA wrapped around a histone protein octamer. The position and histone composition of nucleosomes is governed by ATP-dependent chromatin remodellers such as the 15-subunit INO80 complex. INO80 regulates gene expression, DNA repair and replication ...

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Alternative splicing generates distinct mRNA isoforms and is crucial for proteome diversity in eukaryotes. The RNA-binding protein (RBP) U2AF2 is central to splicing decisions, as it recognizes 3′ splice sites and recruits the spliceosome. We establish “in vitro iCLIP” experiments, in which recombinant RBPs are incubated with long transcripts, to study how U2AF2 ...

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Ultrastable cyclic peptide frameworks offer great potential for drug design due to their improved bioavailability compared to their linear analogues. Using the sunflower trypsin inhibitor-1 (SFTI-1) peptide scaffold in combination with systematic N-methylation of the grafted pharmacophore led to the identification of novel subtype selective melanocortin receptor ...

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NMR spectroscopy at ultra‐high magnetic fields requires improved radiofrequency (rf) pulses to cover the increased spectral bandwidth. Optimized 90° pulse pairs were introduced as Ramsey‐type cooperative (Ram‐COOP) pulses for biomolecular NMR applications. The Ram‐COOP element provides broadband excitation with enhanced sensitivity and reduced artifacts even at ...

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Specific targeting of the integrin subtype α5β1 possesses high potential in cancer diagnosis and therapy. Through sequential N-methylation, we successfully converted the biselective α5β1/αvβ6 peptide c(phg-isoDGR-k) into a potent peptidic RGD binding α5β1 subtype selective ligand c(phg-isoDGR-(NMe)k). Nuclear magnetic resonance spectroscopy and molecular modeling ...

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The epithelial integrin αvβ6 is expressed by many malignant carcinoma cell types, including pancreatic cancer, and thus represents a promising target for radionuclide therapy. The peptide cyclo(FRGDLAFp(NMe)K) was decorated with different chelators (DOTPI, DOTAGA, and DOTA). The Lu(III) complexes of these conjugates exhibited comparable αvβ6 integrin affinities ...

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Solid-state NMR has been employed for characterization of a broad range of biomacromolecules and supramolecular assemblies. However, because of limitations in sensitivity and resolution, the size of the individual monomeric units has rarely exceeded 15 kDa. As such, enzymes, which are often more complex and comprise long peptide chains, have not been easily ...

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