Localization and functional consequences of a direct interaction between TRIOBP-1 and hERG proteins in the heart.

Reduced levels of the cardiac human (h)ERG ion channel protein and the corresponding repolarizing current can cause arrhythmia and sudden cardiac death, but the underlying cellular mechanisms controlling hERG surface expression are not well understood. Here, we identified TRIOBP-1, an F-actin-binding protein previously associated with actin polymerization, as a putative hERG-interacting protein in a yeast-two hybrid screen of a cardiac library. We corroborated this interaction by performing Förster resonance energy transfer (FRET) in HEK293 cells and co-immunoprecipitation in HEK293 cells and native cardiac tissue.

Addition at the molecular level: signal integration in designed Per-ARNT-Sim receptor proteins.

Survival of organisms in dynamic environments requires accurate perception and integration of signals. At the molecular level, signal detection is mediated by signal receptor proteins that largely are of modular composition. Sensor modules, such as the widespread Per-ARNT-Sim (PAS) domains, detect signals and, in response, regulate the biological activity of effector modules.

Structure and function of plant photoreceptors.

Signaling photoreceptors use the information contained in the absorption of a photon to modulate biological activity in plants and a wide range of organisms. The fundamental-and as yet imperfectly answered-question is, how is this achieved at the molecular level? We adopt the perspective of biophysicists interested in light-dependent signal transduction in nature and the three-dimensional structures that underpin signaling. Six classes of photoreceptors are known: light-oxygen-voltage (LOV) sensors, xanthopsins, phytochromes, blue-light sensors using flavin adenine dinucleotide (BLUF), cryptochromes, and rhodopsins.

Structure and signaling mechanism of Per-ARNT-Sim domains.

Per-ARNT-Sim (PAS) domains serve as versatile sensor and interaction modules in signal transduction proteins. PAS sensors detect chemical and physical stimuli and regulate the activity of functionally diverse effector domains. In contrast to this chemical, physical, and functional diversity, the structure of the core of PAS domains is broadly conserved and comprises a five-stranded antiparallel beta sheet and several alpha helices.

Design and signaling mechanism of light-regulated histidine kinases.

Signal transduction proteins are organized into sensor (input) domains that perceive a signal and, in response, regulate the biological activity of effector (output) domains. We reprogrammed the input signal specificity of a normally oxygen-sensitive, light-inert histidine kinase by replacing its chemosensor domain by a light-oxygen-voltage photosensor domain. Illumination of the resultant fusion kinase YF1 reduced net kinase activity by approximately 1000-fold in vitro.

Changes in quaternary structure in the signaling mechanisms of PAS domains.

FixL from Bradyrhizobium japonicum is a PAS sensor protein in which two PAS domains covalently linked to a histidine kinase domain are responsible for regulating nitrogen fixation in an oxygen-dependent manner. The more C-terminal PAS domain, denoted bjFixLH, contains a heme cofactor that binds diatomic molecules such as carbon monoxide and oxygen and regulates the activity of the FixL histidine kinase as part of a two-component signaling system. We present the structures of ferric, deoxy, and carbon monoxide-bound bjFixLH in a new space group ( P1) and at resolutions (1.

Interaction with GM130 during HERG ion channel trafficking. Disruption by type 2 congenital long QT syndrome mutations. Human Ether-à-go-go-Related Gene.

Many mutations in the Human Ether-à-go-go-Related Gene (HERG) cause type 2 congenital long QT syndrome (LQT2) by disrupting trafficking of the HERG-encoded potassium channel. Beyond observations that some mutations trap channels in the endoplasmic reticulum, little is known about how trafficking fails. Even less is known about what checkpoints are encountered in normal trafficking.