The crystal structure of human soluble CD14 reveals a bent solenoid with a hydrophobic amino-terminal pocket.
The crystal structure of human soluble CD14 reveals a bent solenoid with a hydrophobic amino-terminal pocket.
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DOI：
10.4049/jimmunol.1202446
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发表时间：
2013-02-01
期刊：
影响因子：
--
通讯作者：
Tapping RI
中科院分区：
文献类型：
--
作者：
Kelley SL;Lukk T;Nair SK;Tapping RI
人单核细胞分化抗原 CD14 是一种模式识别受体，通过使宿主细胞对细菌脂多糖（LPS；内毒素）、脂蛋白、脂磷壁酸和其他酰化微生物产物敏感，增强对感染的先天免疫反应。 CD14 将这些脂质化微生物产物物理递送至各种 Toll 样受体信号传导复合物，随后在配体结合时诱导细胞内促炎信号传导级联反应。随后的细胞反应通常对宿主有保护作用，但也可能因败血症而导致宿主死亡。在这项工作中，我们确定了人类 CD14 的 X 射线晶体结构。该结构揭示了典型的富含亮氨酸重复蛋白的弯曲螺线管，其氨基末端口袋可能与包括脂多糖在内的酰化配体结合。人类和小鼠 CD14 结构的比较显示整体蛋白质折叠非常相似。然而，与小鼠 CD14 相比，人类 CD14 含有扩大的口袋和替代的边缘残基，这些残基可能对 LPS 结合和细胞激活很重要。本文提出的人 CD14 的 X 射线晶体结构可以促进额外的配体结合结构研究、虚拟对接研究和药物设计工作，以减轻 LPS 诱导的败血症和其他炎症性疾病。
Human monocyte differentiation antigen CD14 is a pattern recognition receptor that enhances innate immune responses to infection by sensitizing host cells to bacterial lipopolysaccharide (LPS; endotoxin), lipoproteins, lipoteichoic acid and other acylated microbial products. CD14 physically delivers these lipidated microbial products to various Toll-like receptor signaling complexes that subsequently induce intracellular proinflammatory signaling cascades upon ligand binding. The ensuing cellular responses are usually protective to the host, but can also result in host fatality through sepsis. In this work, we have determined the X-ray crystal structure of human CD14. The structure reveals a bent solenoid typical of leucine rich repeat proteins with an amino terminal pocket that presumably binds acylated ligands including LPS. Comparison of human and mouse CD14 structures show great similarity in overall protein fold. However, compared to mouse CD14, human CD14 contains an expanded pocket and alternative rim residues that are likely to be important for LPS binding and cell activation. The X-ray crystal structure of human CD14 presented herein may foster additional ligand bound structural studies, virtual docking studies, and drug design efforts to mitigate LPS induced sepsis and other inflammatory diseases.
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影响因子：
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作者：
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DOI：
10.1016/j.bbrc.2008.01.085
发表时间：
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影响因子：
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