Mitochondrial calcium uptake is a critical event in various cellular activities. Two recently identified proteins, the mitochondrial Ca 2+ uniporter (MCU), which is the pore-forming subunit of a Ca 2+ channel, and mitochondrial calcium uptake 1 (MICU1), which is the regulator of MCU, are essential in this event. However, the molecular mechanism by which MICU1 regulates MCU remains elusive. In this study, we report the crystal structures of Ca 2+ -free and Ca 2+ -bound human MICU1. Our studies reveal that Ca 2+ -free MICU1 forms a hexamer that binds and inhibits MCU. Upon Ca 2+ binding, MICU1 undergoes large conformational changes, resulting in the formation of multiple oligomers to activate MCU. Furthermore, we demonstrate that the affinity of MICU1 for Ca 2+ is approximately 15-20 lM. Collectively, our results provide valuable details to decipher the molecular mechanism of MICU1 regulation of mitochondrial calcium uptake.
Oxidative electrochemical pretreatment of carbon fibers greatly Improves their sensitivity for In vivo electrochemical detection of catecholamine species. It Is shown that the extent of the anodic potential excursion In the pretreatment Is a major factor In both the sensitivity and the response time of the resulting fiber electrode. The high sensitivity for neurotransmitter species such as dopamine appears mainly due to adsorption on the oxidized carbon fiber surface states. Practical protocols for fiber electrodes to be used In In vivo brain studies are evaluated.
The key step in meiosis is synaptonemal complex formation, which mediates homologous chromosome alignment and synapsis. False pairing between homologous chromosomes produces infertility. Here, we present a crystal structure of the mouse meiosis-specific protein SYCE3, which is a component of the synaptonemal complex central element. Our studies show that functional SYCE3 most likely forms a dimer or higher order oligomer in cells. Furthermore, we demonstrate that the SYCE3 N-helix interacts with the SYCE1 C-helix, which is another central element component. Our results suggest that helical packing may mediate intra- or inter-association of each central element protein component, thereby playing an essential role in forming the synaptonemal complex central elements.
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