SUMO-2 activity is inhibited by non-covalent interactions with the Aβ peptide: an exploration of potential pathogenic mechanisms in Alzheimer's disease.

SUMOylation is a post-translational modification involving the addition of SUMO isoforms to target proteins and plays a role in various biological processes, including neurodegenerative diseases and ocular pathologies. This study investigates the interaction between SUMO-2 and amyloid (Aβ) peptides, key contributors to Alzheimer's disease, using techniques like cross-linking mass spectrometry, surface plasmon resonance and biolayer interferometry. Data are available via ProteomeXchange with identifier PXD066055.

Protein Secondary Structure Patterns in Short-Range Cross-Link Atlas.

Cross-linking mass spectrometry (XL-MS) has become a powerful tool in structural biology for investigating protein structure, dynamics, and interactomics. However, short-range cross-links, defined as those connecting residues fewer than 20 positions apart, have traditionally been considered less informative and largely overlooked, leaving significant data unexplored in a systematic manner. Here, we present a system-wide analysis of short-range cross-links, demonstrating their intrinsic correlation with protein secondary structure.

Evaluating Imide-Based Mass Spectrometry-Cleavable Cross-Linkers for Structural Proteomics Studies.

Disuccinimidyl dibutyric urea (DSBU) is a mass spectrometry (MS)-cleavable cross-linker that has multiple applications in structural biology, ranging from isolated protein complexes to comprehensive system-wide interactomics. DSBU facilitates a rapid and reliable identification of cross-links through the dissociation of its urea group in the gas phase. In this study, we further advance the structural capabilities of DSBU by remodeling the urea group into an imide, thus introducing a novel class of cross-linkers.

Leveraging Cross-Linking Mass Spectrometry for Modeling Antibody-Antigen Complexes.

Elucidating antibody-antigen complexes at the atomic level is of utmost interest for understanding immune responses and designing better therapies. Cross-linking mass spectrometry (XL-MS) has emerged as a powerful tool for mapping protein-protein interactions, suggesting valuable structural insights. However, the use of XL-MS studies to enable epitope/paratope mapping of antibody-antigen complexes is still limited up to now.

Structural assessment of the full-length wild-type tumor suppressor protein p53 by mass spectrometry-guided computational modeling.

The tetrameric tumor suppressor p53 represents a great challenge for 3D-structural analysis due to its high degree of intrinsic disorder (ca. 40%). We aim to shed light on the structural and functional roles of p53's C-terminal region in full-length, wild-type human p53 tetramer and their importance for DNA binding.

Lighting up Nobel Prize-winning studies with protein intrinsic disorder.

Intrinsically disordered proteins and regions (IDPs and IDRs) and their importance in biology are becoming increasingly recognized in biology, biochemistry, molecular biology and chemistry textbooks, as well as in current protein science and structural biology curricula. We argue that the sequence → dynamic conformational ensemble → function principle is of equal importance as the classical sequence → structure → function paradigm. To highlight this point, we describe the IDPs and/or IDRs behind the discoveries associated with 17 Nobel Prizes, 11 in Physiology or Medicine and 6 in Chemistry.

N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (BOC2) inhibits the angiogenic activity of heparin-binding growth factors.

The peptides N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (BOC2) and BOC-Met-Leu-Phe (BOC1) are widely used antagonists of formyl peptide receptors (FPRs), BOC2 acting as an FPR1/FPR2 antagonist whereas BOC1 inhibits FPR1 only. Extensive investigations have been performed by using these FPR antagonists as a tool to assess the role of FPRs in physiological and pathological conditions. Based on previous observations from our laboratory, we assessed the possibility that BOC2 may exert also a direct inhibitory effect on the angiogenic activity of vascular endothelial growth factor-A (VEGF-A).