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首页> 外文期刊>The FASEB Journal >The minor allele of the missense polymorphism Ser251Pro in perilipin 2 (PLIN2) disrupts an α-helix, affects lipolysis, and is associated with reduced plasma triglyceride concentration in humans
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The minor allele of the missense polymorphism Ser251Pro in perilipin 2 (PLIN2) disrupts an α-helix, affects lipolysis, and is associated with reduced plasma triglyceride concentration in humans

机译：在Perilipin 2（plin2）中畸形多态性Ser251pro的次要等位基因扰乱了α-螺旋，影响脂解，并且与人类中的血浆甘油三酯浓度降低相关

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Perilipin 2 (PLIN2) is the most abundant lipid droplet (LD)-associated protein in nonadipose tissue, and its expression correlates with intracellular lipid accumulation. Here we identified a missense polymorphism, Ser251Pro, that has major effect on protein structure and function, along with an influence on human plasma triglyceride concentration. The evolutionarily conserved Ser251Pro polymorphism was identified with the ClustalW program. Structure modeling using 3D-JigSaw and the Chimera package revealed that the Pro251 allele disrupts a predicted α-helix in PLIN2. Analyses of macrophages from individuals carrying Ser251Pro variants and human embryonic kidney 293 (HEK293) cells stably transfected with either of the alleles demonstrated that the Pro251 variant causes increased lipid accumulation and decreased lipolysis. Analysis of LD size distribution in stably transfected cells showed that the minor Pro251 allele resulted in an increased number of small LDs per cell and increased perilipin 3 protein expression levels as compared with cells carrying the major Ser251 allele. Genotyping of 2113 individuals indicated that the Pro251 variant is associated with decreased plasma triglyceride and very low-density lipoprotein concentrations. Altogether, these data provide the first evidence of a polymorphism in PLIN2 that affects PLIN2 function and may influence the development of metabolic and cardiovascular diseases.—Magné, J., Aminoff, A., Perman Sundelin, J., Mannila, M. N., Gustafsson, P., Hultenby, K., Wernerson, A., Bauer, G., Listenberger, L., Neville, M. J., Karpe, F., Borén, J., Ehrenborg, E. The minor allele of the missense polymorphism Ser251Pro in perilipin 2 (PLIN2) disrupts an α-helix, affects lipolysis, and is associated with reduced plasma triglyceride concentration in humans.
机译：Perilipin 2（plin2）是非脂肪组织中最丰富的脂液滴（LD） - 蛋白质，其表达与细胞内脂质积累相关。在这里，我们鉴定了一种畸形多态性Ser251Pro，对蛋白质结构和功能产生重大影响，以及对人血浆甘油三酯浓度的影响。用Clustalw计划鉴定了进化的Ser251Pro多态性。使用3D-jigsaw和嵌合套餐的结构建模揭示了Pro251等位基因在PLIN2中扰乱了预测的α-螺旋。来自携带Ser251Pro变体的个体的巨噬细胞和人胚胎肾脏293（HEK293）细胞的巨噬细胞稳定地用两种等位基因转染的细胞证明了Pro251变体导致增加的脂质积累和降低脂解。稳定转染细胞中LD尺寸分布的分析表明，与携带主要Ser251等位基因的细胞相比，次次Pro251等位基因导致每种细胞的小LDS数量增加，并且增加了Perilipin 3蛋白表达水平。 2113个体的基因分型表明Pro251变体与降低的血浆甘油三酯和非常低密度的脂蛋白浓度有关。总共，这些数据提供了Plin2中的多态性的第一种证据，这些数据可以影响Plin2功能，并且可能影响代谢和心血管疾病的发展。 - Magné，J.，Aminoff，A.，Persal Sundelin，J.，Mannila，Mn，Gustafsson ，P.，Hultenby，K.，Wernerson，A.，Bauer，G.，Licentberger，L.，Neville，MJ，Karpe，F.，Borén，J.，Ehrenborg，E.麦克斯语多态性Ser251Pro的次要等位基因在Perilipin 2（plin2）中破坏α-螺旋，影响脂解，并且与人类中的血浆甘油三酯浓度降低。

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