Publications by authors named "Frans A A Mulder"
Article Synopsis
- Functional amyloids, essential for the well-being of organisms from bacteria to humans, differ from disease-related amyloids by having their fibrillation regulated by cellular mechanisms and specific sequences, including gatekeeper residues such as Asp.
- Research on the functional amyloid CsgA from E. coli revealed that adding more Asp gatekeepers reduces fibrillation by mainly influencing the initial formation of aggregates, while established fibrils remain stable.
- NMR analysis indicated that even with added gatekeepers, CsgA retains its intrinsically disordered nature; however, there is a notable decrease in transient interactions between monomeric CsgA and its fibrils, showcasing the significance of these interactions in the fibrillation process.
Article Synopsis
- In the mid-20th century, molecular biology and information-communication theory emerged, initially leading to a deep synergy in understanding genetic codes and their meanings.
- Over time, despite advancements, the collaboration between these fields has faced challenges that complicate efforts in next-generation biology, including personalized therapies and protein production.
- To overcome these challenges, a paradigm shift in theoretical biology is necessary, demanding a multidisciplinary approach that incorporates insights from various fields, including Artificial Life.
Article Synopsis
- mCherry is a widely used red fluorescent protein for both live and lab imaging, but concerns about its long-term stability under light exposure persist.
- Understanding how its fluorescence diminishes (quenching) in solution is crucial for improving its photostability through engineering.
- The text presents near-complete NMR chemical shift assignments that could assist researchers in investigating these quenching mechanisms further.
Article Synopsis
- The study examines the link between oxidative stress, cytotoxic oligomers of the protein α-synuclein, and Parkinson's disease development, highlighting potential mechanisms involving lipid peroxidation and membrane disruption.
- Researchers created α-synuclein oligomers in the presence of a lipid peroxidation byproduct and used advanced imaging techniques to study their interaction with live cells.
- Findings show that these oligomers strongly interact with cellular organelles, causing protein immobilization, mitochondrial fragmentation, and associations with endosomal structures, indicating a direct connection between toxic α-syn aggregates and cellular membranes.
Article Synopsis
- * By using a small amount of gadolinium chelate, researchers can enhance high-throughput analysis and accurately determine concentrations, though slow sample temperature regulation still poses challenges.
- * Implementing techniques like reducing scanning times and using equidistant bucketing for metabolomic fingerprinting can significantly improve the efficiency and versatility of NMR in metabolomics.
Solvent paramagnetic relaxation enhancement as a versatile method for studying structure and dynamics of biomolecular systems.
Prog Nucl Magn Reson Spectrosc
December 2022
Article Synopsis
- Solvent paramagnetic relaxation enhancement (sPRE) is an NMR technique that helps analyze the structure and dynamics of biomolecules by studying solvent accessibility of their active nuclei with paramagnetic probes.* -
- This review highlights the recent developments in sPRE applications, detailing its effectiveness in understanding biomolecular properties, interaction surfaces, and conformational changes when combined with other biophysical methods.* -
- The text emphasizes sPRE's potential in enhancing NMR experiment sensitivity and its future applications in areas like NMR metabolomics, drug discovery, and research on intrinsically disordered proteins.*
Article Synopsis
- NMR spin relaxation is a key technique for studying protein dynamics in the fast time scale of picoseconds to nanoseconds.
- Advances in molecular dynamics (MD) simulations have improved our understanding of protein flexibility and dynamics, particularly for backbone motion, but challenges remain in accurately describing side chain dynamics like those of methyl groups.
- This text outlines a new computational method for measuring cross-correlation relaxation parameters of methyl groups in proteins, showing that MD simulations align well with experimental data, particularly in the case of ubiquitin using different force fields.
Probiotic bacteria are increasingly popular as dietary supplements and have the potential as alternatives to traditional antibiotics. We have recently shown that pretreatment with spp. Lb21 increases the life span of and results in resistance toward pathogenic methicillin-resistant (MRSA).
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- RoxP is a protein produced by a common skin bacterium that helps protect cells from damage caused by free radicals, suggesting it could improve skin barrier function.
- The study aimed to understand RoxP's structure and how it works as an antioxidant, revealing its unique shape and positively charged groove that may bind beneficial molecules.
- Despite looking similar to proteins that help cells stick together, RoxP doesn't aid in bacterial adhesion to skin cells; instead, specific parts of its structure are linked to its antioxidant properties.
Article Synopsis
- Solution-state NMR relaxation experiments help study protein dynamics at a detailed atomic level, particularly on rapid timescales.
- Research on T4 lysozyme using molecular dynamics simulations reveals that most backbone entropy is associated with quick dynamics, while slower dynamics of side chains contribute significantly to conformational entropy.
- Understanding these dynamics is crucial for accurately determining thermodynamic properties of proteins.
Article Synopsis
- - The study investigates how lipid peroxidation products 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE) affect the aggregation of α-synuclein (αSN), a protein linked to Parkinson's disease, showing that αSN oligomer stability and yield increase in the presence of these products.
- - ONE is found to be more effective than HNE in inducing αSN aggregation, leading to differences in the size and shape of the resulting αSN oligomers (αSO), with ONE-αSO generally being smaller than HNE-αSO.
- - The research highlights the significance of the His50 residue in αSN aggregation, showing that
Article Synopsis
- The study investigates the impact of electrostatics on hydrogen exchange (HX) in the unfolded state of proteins, emphasizing its importance for understanding protein stability and dynamics.
- Using the disordered protein α-synuclein as a case study, researchers developed a method to calculate electrostatic potential along the protein chain, providing quantitative insights.
- Findings indicate that the C-terminal region of α-synuclein experiences a significant reduction in hydroxide concentration, which correlates with NMR spectroscopy data, suggesting that reduced HX is not due to hydrogen bonding or structural formation.
Article Synopsis
- NMR chemical shifts are sensitive indicators of local protein structure, and new techniques for predicting random coil chemical shifts have improved our ability to detect small structural variations.
- CheSPI is a user-friendly method that analyzes these chemical shifts to identify and classify both ordered and disordered protein regions, revealing subtle structural differences among proteins.
- Available for free online or as a Python program, CheSPI generates detailed numeric and graphical outputs, making it easy to understand and visualize protein structures with clear examples.
Article Synopsis
- * (-)-epigallocatechin gallate (EGCG) has been identified as a potential modulator that reduces αSN's harmful effects by binding effectively to the protein and stabilizing it during oligomerization.
- * Studies using NMR spectroscopy reveal that EGCG binds more strongly to the monomeric form of αSN, and even small amounts of EGCG can significantly decrease the toxicity of αSN oligomers, suggesting a cooperative effect between protein and EGCG interactions.
Article Synopsis
- * A study analyzed 2,628 plots of 565 spring malting barley lines focusing on six malting quality traits, while collecting 24,018 metabolomic features through NMR spectroscopy.
- * Results indicated that about one-third of the metabolomic features were heritable, with significant genetic and phenotypic correlations to malting quality traits, highlighting their potential in barley breeding efforts.
Article Synopsis
- Structural disorder in eukaryotic proteins is essential for various biological functions, but predicting the degree of order and disorder from amino acid sequences is complex.
- The researchers utilized the CheZOD database to develop ODiNPred, a sequence-based predictor that analyzes protein order/disorder using deep neural networks and NMR chemical shift data.
- ODiNPred outperforms existing predictors by effectively forecasting variations in protein disorder, especially for intermediate disorder, by incorporating both sequence and evolutionary features.
Article Synopsis
- The text outlines a method for simplifying 2D constant-time C-H heteronuclear single-quantum correlation (HSQC) spectra in C-enriched proteins.
- This method uses a single pulse sequence to capture eight sub-spectra based on the specific characteristics of the NMR signals related to spin topology.
- The resulting five sets of spectra allow for clearer differentiation of C-H correlations among various amino acids, making it easier to analyze and assign resonance peaks, useful for structure determination in NMR experiments.
Article Synopsis
- Understanding hydrogen exchange kinetics in proteins helps explain their structure and behavior.
- The chapter introduces a new method called Paris-DÉCOR for measuring fast hydrogen exchange rates in proteins using NMR spectroscopy.
- It includes a detailed protocol for conducting the experiment along with MATLAB scripts for analyzing the numerical data related to exchange rates.
Article Synopsis
- Disorder plays a crucial role in the function of many proteins, and the variation in their disordered regions highlights the complexity of intrinsically disordered proteins (IDPs).
- A promising approach to better understanding IDPs is through quantitative characterization, particularly using nuclear magnetic resonance (NMR) spectroscopy.
- The Chemical shift Z-score for assessing Order/Disorder (CheZOD Z-score) is introduced as a method to measure the balance between order and disorder in proteins, with easy calculation options available via Python or online submission.
Article Synopsis
- Phenomycin is a small bacterial protein with 89 amino acids that is toxic to mammalian cells and inhibits ribosome function, affecting translation initiation.
- The study reveals that the toxicity of phenomycin is linked to its direct inhibition of protein translation and that effective cellular uptake is hindered by endosomal escape.
- Researchers used high-resolution NMR spectroscopy to analyze phenomycin’s structure and found a specific peptide segment crucial for its toxic effects through comparisons with similar proteins.
Article Synopsis
- NMR spin relaxation experiments and molecular dynamics (MD) simulations are key techniques for studying protein dynamics at very short time scales, offering complementary insights when compared appropriately.
- Recent studies revealed that inaccurate energy barriers for methyl group rotations in certain MD simulations led to discrepancies in predicted NMR relaxation rates, particularly for the AMBER ff99SB-ILDN force field.
- The integration of accurate quantum chemical calculations into MD force fields, like CHARMM36 and AMBER ff15ipq, improved the modeling of methyl group dynamics, resulting in NMR relaxation data that closely matched experimental results, highlighting advancements in MD simulations for studying protein dynamics.
How internal cavities destabilize a protein.
Mengjun Xue Takuro Wakamoto Camilla Kejlberg Yuichi Yoshimura Tania Aaquist Nielsen Frans A A Mulder
Proc Natl Acad Sci U S A
October 2019
Article Synopsis
- Proteins have a structured shape but can shift into less stable, excited states due to thermal energy, which are crucial for their biological functions.
- Using NMR spectroscopy alongside pressure changes, researchers can study these elusive excited states and observe how pressure influences protein structures.
- The study revealed how specific protein regions respond to pressure, leading to the discovery of previously hidden folded states and calculating the energetic cost of empty spaces within the protein structure.
Fast and Quantitative NMR Metabolite Analysis Afforded by a Paramagnetic Co-Solute.
Angew Chem Int Ed Engl
October 2019
Article Synopsis
- - NMR spectroscopy is a crucial technique for identifying and analyzing the structure of small molecules, valued for its reliability and quantitative capabilities in various fields like chemical synthesis and metabolomics.
- - A major drawback of traditional NMR is the slow recovery of nuclear spin alignment, leading to wasted experimental time, especially in quantitative NMR where lengthy waiting periods are required.
- - The introduction of paramagnetic gadolinium chelate can significantly improve efficiency and reduce waiting times, allowing for faster and cost-effective high-throughput mixture analysis.
Article Synopsis
- - Understanding protein disorder is crucial for biological functions, but accurately predicting this disorder from protein sequences is challenging due to a lack of calibration in existing prediction methods.
- - Researchers created a new benchmarking set using NMR chemical shift data to evaluate the effectiveness of 26 popular disorder prediction methods.
- - The analysis revealed significant variability in the performance of these methods, with some showing a tendency to over-predict order, impacting how protein disorder is interpreted, especially in proteome studies.