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具有完整功能的标记朊病毒蛋白的全面天然相互作用组。

The comprehensive native interactome of a fully functional tagged prion protein.

作者信息

Rutishauser Dorothea, Mertz Kirsten D, Moos Rita, Brunner Erich, Rülicke Thomas, Calella Anna Maria, Aguzzi Adriano

机构信息

Institute of Neuropathology, University Hospital of Zurich, Zurich, Switzerland.

出版信息

PLoS One. 2009;4(2):e4446. doi: 10.1371/journal.pone.0004446. Epub 2009 Feb 11.

DOI:10.1371/journal.pone.0004446
PMID:19209230
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2635968/
Abstract

The enumeration of the interaction partners of the cellular prion protein, PrP(C), may help clarifying its elusive molecular function. Here we added a carboxy proximal myc epitope tag to PrP(C). When expressed in transgenic mice, PrP(myc) carried a GPI anchor, was targeted to lipid rafts, and was glycosylated similarly to PrP(C). PrP(myc) antagonized the toxicity of truncated PrP, restored prion infectibility of PrP(C)-deficient mice, and was physically incorporated into PrP(Sc) aggregates, indicating that it possessed all functional characteristics of genuine PrP(C). We then immunopurified myc epitope-containing protein complexes from PrP(myc) transgenic mouse brains. Gentle differential elution with epitope-mimetic decapeptides, or a scrambled version thereof, yielded 96 specifically released proteins. Quantitative mass spectrometry with isotope-coded tags identified seven proteins which co-eluted equimolarly with PrP(C) and may represent component of a multiprotein complex. Selected PrP(C) interactors were validated using independent methods. Several of these proteins appear to exert functions in axomyelinic maintenance.

摘要

细胞朊蛋白PrP(C)相互作用伙伴的列举，可能有助于阐明其难以捉摸的分子功能。在此，我们在PrP(C)的羧基近端添加了一个myc表位标签。当在转基因小鼠中表达时，PrP(myc)带有糖基磷脂酰肌醇（GPI）锚定，靶向脂筏，并且与PrP(C)类似地进行糖基化。PrP(myc)拮抗截短型PrP的毒性，恢复PrP(C)缺陷小鼠的朊病毒感染性，并物理性地整合到PrP(Sc)聚集体中，表明它具有真正PrP(C)的所有功能特性。然后，我们从PrP(myc)转基因小鼠大脑中免疫纯化含myc表位的蛋白复合物。用模拟表位的十肽或其乱序版本进行温和的差异洗脱，得到96种特异性释放的蛋白。使用同位素编码标签的定量质谱法鉴定出七种与PrP(C)等摩尔共洗脱的蛋白，它们可能代表多蛋白复合物的组分。使用独立方法对选定的PrP(C)相互作用蛋白进行了验证。其中几种蛋白似乎在轴突髓鞘维持中发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec28/2635968/41fef0a124c3/pone.0004446.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec28/2635968/7f67a0e8858b/pone.0004446.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec28/2635968/14a9a2e1fd30/pone.0004446.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec28/2635968/26f0cd62e113/pone.0004446.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec28/2635968/41fef0a124c3/pone.0004446.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec28/2635968/7f67a0e8858b/pone.0004446.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec28/2635968/14a9a2e1fd30/pone.0004446.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec28/2635968/26f0cd62e113/pone.0004446.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec28/2635968/41fef0a124c3/pone.0004446.g004.jpg

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2
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3
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4
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7
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8
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