Mechanism of acid-sensing ion channel modulation by Hi1a.

Acid-sensing ion channels (ASICs) are trimeric cation-selective channels activated by extracellular acidification. Amongst many pathological roles, ASICs are an important mediator of ischemic cell death and hence an attractive drug target for stroke treatment as well as other conditions. A peptide called Hi1a, isolated from Australian funnel web spider venom, inhibits ASIC1a and attenuates cell death in a stroke model up to 8 h after stroke induction.

Topography and motion of acid-sensing ion channel intracellular domains.

Acid-sensing ion channels (ASICs) are trimeric cation-selective channels activated by decreases in extracellular pH. The intracellular N and C terminal tails of ASIC1 influence channel gating, trafficking, and signaling in ischemic cell death. Despite several X-ray and cryo-EM structures of the extracellular and transmembrane segments of ASIC1, these important intracellular tails remain unresolved.

Nuclear Magnetic Resonance of Single-Stranded RNAs and DNAs of CAAU and UCAAUC as Benchmarks for Molecular Dynamics Simulations.

RNA and DNA are rapidly emerging as targets for therapeutics and as potential frameworks for nanotechnology. Accurate methods for predicting and designing structures and dynamics of nucleic acids would accelerate progress in these and other applications. Suitable approximations for modeling nucleic acids are being developed but require validation against disparate experimental observations.

Nuclear Magnetic Resonance Reveals That GU Base Pairs Flanking Internal Loops Can Adopt Diverse Structures.

RNA thermodynamics play an important role in determining the two- and three-dimensional structures of RNA. Internal loops of the sequence 5'-GMNU/3'-UNMG are relatively unstable thermodynamically. Here, five duplexes with GU-flanked 2 × 2 nucleotide internal loops were structurally investigated to reveal determinants of their instability.

Improving RNA nearest neighbor parameters for helices by going beyond the two-state model.

RNA folding free energy change nearest neighbor parameters are widely used to predict folding stabilities of secondary structures. They were determined by linear regression to datasets of optical melting experiments on small model systems. Traditionally, the optical melting experiments are analyzed assuming a two-state model, i.

Surprising Sequence Effects on GU Closure of Symmetric 2 × 2 Nucleotide RNA Internal Loops.

GU base pairs are important RNA structural motifs and often close loops. Accurate prediction of RNA structures relies upon understanding the interactions determining structure. The thermodynamics of some 2 × 2 nucleotide internal loops closed by GU pairs are not well understood.