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The atrial natriuretic peptide (ANP) hormone is secreted by the heart in response to an increase in blood pressure. ANP exhibits several potent anti-hypertensive actions in the kidney, adrenal gland and vascular system. These actions are induced by hormone binding extracellularly to the ANP receptor, thereby activating its intracellular guanylyl cyclase domain for the production of cyclic GMP. Here we present the crystal structure of the glycosylated dimerized hormone-binding domain of the ANP receptor at 2.0-A resolution. The monomer comprises two interconnected subdomains, each encompassing a central beta-sheet flanked by alpha-helices, and exhibits the type I periplasmic binding protein fold. Dimerization is mediated by the juxtaposition of four parallel helices, arranged two by two, which brings the two protruding carboxy termini into close relative proximity. From affinity labelling and mutagenesis studies, the ANP-binding site maps to the side of the dimer crevice and extends to near the dimer interface. A conserved chloride-binding site is located in the membrane distal domain, and we found that hormone binding is chloride dependent. These studies suggest mechanisms for hormone activation and the allostery of the ANP receptor. 相似文献
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Speciation through sensory drive in cichlid fish 总被引:1,自引:0,他引:1
Seehausen O Terai Y Magalhaes IS Carleton KL Mrosso HD Miyagi R van der Sluijs I Schneider MV Maan ME Tachida H Imai H Okada N 《Nature》2008,455(7213):620-626
Theoretically, divergent selection on sensory systems can cause speciation through sensory drive. However, empirical evidence is rare and incomplete. Here we demonstrate sensory drive speciation within island populations of cichlid fish. We identify the ecological and molecular basis of divergent evolution in the cichlid visual system, demonstrate associated divergence in male colouration and female preferences, and show subsequent differentiation at neutral loci, indicating reproductive isolation. Evidence is replicated in several pairs of sympatric populations and species. Variation in the slope of the environmental gradients explains variation in the progress towards speciation: speciation occurs on all but the steepest gradients. This is the most complete demonstration so far of speciation through sensory drive without geographical isolation. Our results also provide a mechanistic explanation for the collapse of cichlid fish species diversity during the anthropogenic eutrophication of Lake Victoria. 相似文献
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Résumé Les cellules ascites de la tumeur Ehrlich couvaient in vitro avec le précurseur radioactif de l'hémine-aminolévulinic acid-4-C14. Les préparations de ARN du foie de la souris stimulaient le niveau de synthèse de l'hémine. 相似文献
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