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Rasmussen SG Choi HJ Rosenbaum DM Kobilka TS Thian FS Edwards PC Burghammer M Ratnala VR Sanishvili R Fischetti RF Schertler GF Weis WI Kobilka BK 《Nature》2007,450(7168):383-387
Structural analysis of G-protein-coupled receptors (GPCRs) for hormones and neurotransmitters has been hindered by their low natural abundance, inherent structural flexibility, and instability in detergent solutions. Here we report a structure of the human beta2 adrenoceptor (beta2AR), which was crystallized in a lipid environment when bound to an inverse agonist and in complex with a Fab that binds to the third intracellular loop. Diffraction data were obtained by high-brilliance microcrystallography and the structure determined at 3.4 A/3.7 A resolution. The cytoplasmic ends of the beta2AR transmembrane segments and the connecting loops are well resolved, whereas the extracellular regions of the beta2AR are not seen. The beta2AR structure differs from rhodopsin in having weaker interactions between the cytoplasmic ends of transmembrane (TM)3 and TM6, involving the conserved E/DRY sequences. These differences may be responsible for the relatively high basal activity and structural instability of the beta2AR, and contribute to the challenges in obtaining diffraction-quality crystals of non-rhodopsin GPCRs. 相似文献
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The terrestrial and lunar cratering rate is often assumed to have been nearly constant over the past 3 Gyr. Different lines of evidence, however, suggest that the impact flux from kilometre-sized bodies increased by at least a factor of two over the long-term average during the past approximately 100 Myr. Here we argue that this apparent surge was triggered by the catastrophic disruption of the parent body of the asteroid Baptistina, which we infer was a approximately 170-km-diameter body (carbonaceous-chondrite-like) that broke up 160(-20)+30Myr ago in the inner main asteroid belt. Fragments produced by the collision were slowly delivered by dynamical processes to orbits where they could strike the terrestrial planets. We find that this asteroid shower is the most likely source (>90 per cent probability) of the Chicxulub impactor that produced the Cretaceous/Tertiary (K/T) mass extinction event 65 Myr ago. 相似文献
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