GPCR proteins represent the largest family of signaling membrane proteins in eukaryotic cells.Their importance to basic cell biology,human diseases,and pharma-ceutical interventions is well established.Many crystal st...GPCR proteins represent the largest family of signaling membrane proteins in eukaryotic cells.Their importance to basic cell biology,human diseases,and pharma-ceutical interventions is well established.Many crystal structures of GPCR proteins have been reported in both active and inactive conformations.These data indicate that agonist binding alone is not suffi cient to trigger the conformational change of GPCRs necessary for binding of downstream G-proteins,yet other essential factors re-main elusive.Based on analysis of available GPCR crystal structures,we identifi ed a potential conformational switch around the conserved Asp2.50,which consistently shows distinct conformations between inactive and active states.Combining the structural information with the current literature,we propose an energy-coupling mechanism,in which the interaction between a charge change of the GPCR protein and the membrane potential of the living cell plays a key role for GPCR activation.展开更多
Dear Editor,Mitochondrial Ca2+homeostasis regulates energy production,cell division,and cell death.The basic properties of mitochondrial Ca2+uptake have been firmly established.The Ca2+influx is mediated by MCU,driven...Dear Editor,Mitochondrial Ca2+homeostasis regulates energy production,cell division,and cell death.The basic properties of mitochondrial Ca2+uptake have been firmly established.The Ca2+influx is mediated by MCU,driven by membrane potential and using a uniporter mechanism(Vasington and Murphy,1962).Patch-clamp analysis of MCU currents demonstrated that MCU is a channel with exceptionally high Ca2+selectivity(Kirichok et al.,2004).展开更多
基金the National Basic Research Program(973 Program)to XCZ(Nos.2009CB918803 and 2011CB910301).
文摘GPCR proteins represent the largest family of signaling membrane proteins in eukaryotic cells.Their importance to basic cell biology,human diseases,and pharma-ceutical interventions is well established.Many crystal structures of GPCR proteins have been reported in both active and inactive conformations.These data indicate that agonist binding alone is not suffi cient to trigger the conformational change of GPCRs necessary for binding of downstream G-proteins,yet other essential factors re-main elusive.Based on analysis of available GPCR crystal structures,we identifi ed a potential conformational switch around the conserved Asp2.50,which consistently shows distinct conformations between inactive and active states.Combining the structural information with the current literature,we propose an energy-coupling mechanism,in which the interaction between a charge change of the GPCR protein and the membrane potential of the living cell plays a key role for GPCR activation.
文摘Dear Editor,Mitochondrial Ca2+homeostasis regulates energy production,cell division,and cell death.The basic properties of mitochondrial Ca2+uptake have been firmly established.The Ca2+influx is mediated by MCU,driven by membrane potential and using a uniporter mechanism(Vasington and Murphy,1962).Patch-clamp analysis of MCU currents demonstrated that MCU is a channel with exceptionally high Ca2+selectivity(Kirichok et al.,2004).
