Bond PJ
The disordered plant dehydrin Lti30 protects the membrane during water-related stress by cross-linking lipids
Dehydrins are intrinsically disordered proteins, generally expressed in plants as a response to embryogenesis and water-related stress. Their suggested functions are in membrane stabilization and cell protection. All dehydrins contain at least one copy of the highly conserved K-segment, proposed to be a membrane binding motif.
ReadInfectivity of Dengue Virus Serotypes 1 and 2 Is Correlated with E-Protein Intrinsic Dynamics but Not to Envelope Conformations
Dengue is a mosquito-borne virus with dire health and economic impacts. Dengue is responsible for an estimated 390 million infections per year, with dengue 2 (DENV2) being the most virulent strain among the four serotypes. Interestingly, it is also in strains of this serotype that temperature-dependent large-scale morphological changes, termed “breathing,” have been observed.
ReadDirecting GDNF-mediated neuronal signaling with proactively programmable cell-surface saccharide-free glycosaminoglycan mimetics
A significant barrier to harnessing the power of cell-surface glycosaminoglycans (GAGs) to modulate glial cell-line-derived neurotrophic factor (GDNF) signaling is the difficulty in accessing key GAG structures involved. Here, we report tailored GDNF signaling using synthetic polyproline-based GAG mimetics (PGMs).
ReadEnergetic Fingerprinting of Ligand Binding to Paralogous Proteins: The Case of the Apoptotic Pathway
Networks of biological molecules are key to cellular function, governing processes ranging from signal cascade propagation to metabolic pathway regulation. Genetic duplication processes give rise to sets of regulatory proteins that have evolved from a common ancestor, leading to interactomes whose dysregulation is often associated with disease. A better understanding of the determinants of specificity at 21 interfaces shared by functionally related proteins is crucial to the rational design of novel pharmacotherapeutic agents.
ReadEngineering an Osmosensor by Pivotal Histidine Positioning within Disordered Helices
Histidine kinases (HKs) funnel diverse environmental stimuli into a single autophosphorylation event at a conserved histidine residue. The HK EnvZ is a global sensor of osmolality and cellular acid pH. In previous studies, we discovered that osmosensing in EnvZ was mediated through osmolyte-induced stabilization of the partially disordered helical backbone spanning the conserved histidine autophosphorylation site (His243).
ReadMechanism of Enhanced Immature Dengue Virus Attachment to Endosomal Membrane Induced by prM Antibody
Dengue virus (DENV) particles are released from cells in different maturation states. Fully immature DENV (immDENV) is generally non-infectious, but can become infectious when complexed with anti-precursor membrane (prM) protein antibodies. It is unknown how anti-prM antibody-coated particles can undergo membrane fusion since the prM caps the envelope (E) protein fusion loop.
ReadSingle-molecule studies of flavivirus envelope dynamics: Experiment and computation
Flaviviruses are simple enveloped viruses exhibiting complex structural and functional heterogeneities. Decades of research have provided crucial basic insights, antiviral medication and moderately successful gene therapy trials. The most infectious particle is, however, not always the most abundant one in a population, questioning the utility of classic ensemble-averaging virology approaches. Indeed, viral replication is often not particularly efficient, prone to errors or containing parallel routes.
ReadFacile saccharide-free mimetics that recapitulate key features of glycosaminoglycan sulfation patterns
Controlling glycosaminoglycan (GAG) activity to exploit its immense potential in biology ultimately requires facile manipulation of sulfation patterns associated with GAGs. However, satisfying this requirement in full remains challenging, given that synthesis of GAGs is technically arduous while convenient GAG mimetics often produce sulfation patterns that are uncharacteristic of GAGs.
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