Protein arginine methyltransferase (PRMT) 5 is an essential arginine methyltransferase responsible for the majority of cellular symmetric dimethyl-arginine (SDMA) marks. PRMT5 uses substrate adaptors such as pICln, RIOK1, and COPR5, to recruit and methylate a wide range of substrates. Although the substrate adaptors play important roles in substrate recognition, how they direct PRMT5 activity towards specific substrates remains incompletely understood.
View Article and Find Full Text PDFThe evolution of bipedal gait is a key adaptive feature in hominids, but the running abilities of early hominins have not been extensively studied. Here, we present physics simulations of Australopithecus afarensis that demonstrate this genus was mechanically capable of bipedal running but with absolute and relative (size-normalized) maximum speeds considerably inferior to modern humans. Simulations predicted running energetics for Australopithecus that are generally consistent with values for mammals and birds of similar body size, therefore suggesting relatively low cost of transport across a limited speed range.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
November 2024
Bifunctional molecules such as targeted protein degraders induce proximity to promote gain-of-function pharmacology. These powerful approaches have gained broad traction across academia and the pharmaceutical industry, leading to an intensive focus on strategies that can accelerate their identification and optimization. We and others have previously used chemical proteomics to map degradable target space, and these datasets have been used to develop and train multiparameter models to extend degradability predictions across the proteome.
View Article and Find Full Text PDFA locomotor system that can function across different environmental conditions and produce a range of performances is one of the most critical abilities needed for extant and extinct animals in order to survive and maximise their competitive fitness. Recent engineering-inspired paleontological studies have reconstructed feasible locomotor patterns in extinct animals. However, it is still challenging to describe how extinct animals successfully adjust their locomotor patterns to new situations (e.
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