Crystal Structure of a Lipid G Protein-Coupled Receptor
Crystal Structure of a Lipid G Protein-Coupled Receptor
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DOI：
10.1126/science.1244693
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发表时间：
2012-02-17
期刊：
影响因子：
56.9
通讯作者：
Stevens, Raymond C.
中科院分区：
文献类型：
--
作者：
Hanson, Michael A.;Roth, Christopher B.;Stevens, Raymond C.
尽管认识到森林生态系统服务的重要性，但缺乏对全球森林变化的量化。在这项研究中，利用地球观测卫星数据绘制了2000年至2012年全球森林损失(230万平方公里)和增加(80万平方公里)的地图，空间分辨率为30米。热带地区是唯一显示出这种趋势的气候领域，森林损失每年增加2101平方公里。巴西有据可查的森林砍伐减少被印度尼西亚、马来西亚、巴拉圭、玻利维亚、赞比亚、安哥拉和其他地方森林损失的增加所抵消。亚热带森林内实行的集约化林业导致了全球最高的森林变化率。从绝对值和比例来看，北方森林的损失主要是由于火灾和林业造成的，仅次于热带地区。这些结果描述了一个全球一致和局部相关的森林变化记录。溶血磷脂1-磷酸鞘氨醇通过激活G蛋白偶联的1-磷酸鞘氨醇受体调节淋巴细胞运输、内皮发育和完整性、心率以及血管张力和成熟。在这里，我们提出了神经鞘氨醇1-磷酸受体1与T4-溶菌酶(S1P(1)-T4L)在模拟鞘氨醇拮抗剂的复合体中的晶体结构。细胞外进入结合口袋的通道被受体的氨基末端和胞外环所阻断。在受体的跨膜区内，配体侧向进入螺旋I和VII之间，从而获得通道。这种结构，连同诱变、激动剂结构-活性关系数据和建模，提供了激活S1P(1)的分子识别和疏水体积需求的详细视图，从而导致免疫和基质细胞反应的调节。
Quantification of global forest change has been lacking despite the recognized importance of forest ecosystem services. In this study, Earth observation satellite data were used to map global forest loss (2.3 million square kilometers) and gain (0.8 million square kilometers) from 2000 to 2012 at a spatial resolution of 30 meters. The tropics were the only climate domain to exhibit a trend, with forest loss increasing by 2101 square kilometers per year. Brazil's well-documented reduction in deforestation was offset by increasing forest loss in Indonesia, Malaysia, Paraguay, Bolivia, Zambia, Angola, and elsewhere. Intensive forestry practiced within subtropical forests resulted in the highest rates of forest change globally. Boreal forest loss due largely to fire and forestry was second to that in the tropics in absolute and proportional terms. These results depict a globally consistent and locally relevant record of forest change.The lyso-phospholipid sphingosine 1-phosphate modulates lymphocyte trafficking, endothelial development and integrity, heart rate, and vascular tone and maturation by activating G protein-coupled sphingosine 1-phosphate receptors. Here, we present the crystal structure of the sphingosine 1-phosphate receptor 1 fused to T4-lysozyme (S1P(1)-T4L) in complex with an antagonist sphingolipid mimic. Extracellular access to the binding pocket is occluded by the amino terminus and extracellular loops of the receptor. Access is gained by ligands entering laterally between helices I and VII within the transmembrane region of the receptor. This structure, along with mutagenesis, agonist structure-activity relationship data, and modeling, provides a detailed view of the molecular recognition and requirement for hydrophobic volume that activates S1P(1), resulting in the modulation of immune and stromal cell responses.