【摘 要】
:
Large-conductance Ca2+-and voltage-activated BK channels, composed of poreforming subunits and auxiliary β subunits, play important roles in diverse physiological activities.The β1 is predominately ex
【机 构】
:
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Tec
【出 处】
:
The 9th Asian Biophysics Association Symposium (ABA2015)(第九届
论文部分内容阅读
Large-conductance Ca2+-and voltage-activated BK channels, composed of poreforming subunits and auxiliary β subunits, play important roles in diverse physiological activities.The β1 is predominately expressed in smooth muscle cells, where it greatly enhances the Ca2+ sensitivity of BK channels for proper regulation of smooth muscle tone.However, structural basis underlying dynamic interaction between BK mSlo1 and β1 remains elusive.Using macroscopic ionic current recordings in various Ca2+ and Mg2+ concentrations, we identified two binding sites on the cytosolic N-terminal of β1,namely the electrostatic enhancing (E) site (mSlo1(K392,R393)∶∶β1(E13,T14)), increasing the calcium sensitivity of BK channels, and the hydrophobic (H) site (mSlo1(L906,L 908)∶∶β1(L5,V6,M7)), passing the physical force from the Ca2+ bowl onto the E site and S6 C-linker.Dynamic binding of these sites affects the interaction between the cytosolic domain (CTD) and voltage sensing domain(VSD), leading to the reduction of Mg2+ sensitivity.A comprehensive structural model of the BK(mSlo1 □/β1) complex was reconstructed based on these functional studies, which provides structural and mechanistic insights for understanding BK gating.
其他文献
Glycogen Storage Disorder Type la (GSD1a), also known as von Gierkes disease, is the most common Glycogen Storage Disorder.It is caused by loss of function of Glucose-6-Phosphatase (G6PC), the enzyme
Plasmodium falciparum, the most fatal causative agent of human malaria, undergoes major remodeling of subcellular structures during its development and encounters various conditions such as nutrient l
Autophagy is dispensable for lipids utilization to maintain the cellular energy hemostasis.Previous works show that autophagy is involved in lipid metabolism, whereas the underlying mechanism is uncle
Autophagy is the major intracellular catabolic mechanism by which cytoplasmic materials can be degraded in the lysosome.Although physiological levels of autophagy are essential for normal cellular hom
Background:Neither glucose nor FFA alone cause clinically meaningful pancreatic β-cell toxicity, especially in subjects with normal or glucose intolerance.The down-and up-regulations of autophagy unde
Wolfram syndrome (DIDMOAD;WS) is a genetic disorder characterized by diabetes insipidus,diabetes mellitus, optical atrophy, deafness and brain atrophy that results in death in middle adulthood, typica
Background Hirschsprungs disease (HD) is common congenital gastrointestinal malformation,characterized by the lack of neurons from distal rectum to proximal bowel.Autophagy, a conserved lysosomal degr
Autophagy is a major cellular machinery for the degradation of aggregated proteins via lysosome.Autophagy deregulation is closely associated with neurodegenerative and inflammatory disorders.Schisandr
Lysosomes are membrane-bound acidic organelles that degrade cargoes derived from endocytosis, phagocytosis or autophagy through the action of a variety of lysosomal hydrolases.The degradation products
Fundamental and evolutionarily conserved role of autophagy is adaptation to starvation,however, the exact role of autophagy as nutrient recycle system remains unclear in mammals.We have investigated t