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Protein folding is the process by which proteins achieve their mature functional (native) tertiary structure, and often begins co-translationally. Protein folding requires chaperones and often involves stepwise establishment of regular secondary and supersecondary structures, namely α-helices and β-sheets, that fold rapidly, stabilized by hydrogen bonding and disulphide bridges, and then tertiary structure.
Researchers mimic protein interface helices by stapling peptide side chains, or replacing hydrogen bonds with covalent ones, and synthetic helical mimics are heavily biased towards stapling. Here the authors describe bioinformatic discovery of hydrophobic triangles at helix N-termini, and rigid, bicyclic synthetic mimics of them.
OpenFold is a trainable open-source implementation of AlphaFold2. It is fast and memory efficient, and the code and training data are available under a permissive license.
The details of how the protein folding and degradation systems collaborate to combat potentially toxic non-native proteins are unknown. Here the authors perform systematic studies of missense and nonsense variants of the cytosolic aspartoacylase, ASPA, where loss-of-function variants are linked to Canavan disease.
The techniques available for comparing protein structures do not focus directly on the chemical nature of residue environments. Here, authors describe a computational method that can capture both the spatial and chemical dissimilarities of residue surroundings.
Aviner et al. show that translation and aggregation of Huntingtin (HTT) are regulated by a stress-responsive upstream open reading frame. Mutant HTT depletes translation elongation factor eIF5A, leading to ribosome pausing and collisions.
Claire Durrant reminds us of the importance of studying the physiological roles of proteins and their aggregates to understand their roles in disease and inform therapies, discussing a 2008 paper on amyloid-β from the Arancio lab.
Natural protein folding takes place in aqueous cell environments. Now, it has been found that proteins in a water-free environment undergo faster and more efficient folding.