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3型腺病毒十二面体的RGD环包含一个影响整合素结合的硫酸乙酰肝素蛋白聚糖结合位点。

The adenovirus type 3 dodecahedron's RGD loop comprises an HSPG binding site that influences integrin binding.

作者信息

Gout E, Schoehn G, Fenel D, Lortat-Jacob H, Fender P

机构信息

CNRS-Institut de Biologie Structurale, 41 rue Jules Horowitz, 38027 Grenoble, France.

出版信息

J Biomed Biotechnol. 2010;2010:541939. doi: 10.1155/2010/541939. Epub 2010 Mar 4.

DOI:10.1155/2010/541939
PMID:20224646
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2833306/
Abstract

Human type 3 adenovirus dodecahedron (a virus like particle made of twelve penton bases) features the ability to enter cells through Heparan Sulphate Proteoglycans (HSPGs) and integrins interaction and is used as a versatile vector to deliver DNA or proteins. Cryo-EM reconstruction of the pseudoviral particle with Heparan Sulphate (HS) oligosaccharide shows an extradensity on the RGD loop. A set of mutants was designed to study the respective roles of the RGD sequence (RGE mutant) and of a basic sequence located just downstream. Results showed that the RGE mutant binding to the HS deficient CHO-2241 cells was abolished and unexpectedly, mutation of the basic sequence (KQKR to AQAS) dramatically decreased integrin recognition by the viral pseudoparticle. This basic sequence is thus involved in integrin docking, showing a close interplay between HSPGs and integrin receptors.

摘要

人3型腺病毒十二面体（一种由十二个五聚体基底构成的病毒样颗粒）具有通过硫酸乙酰肝素蛋白聚糖（HSPGs）和整合素相互作用进入细胞的能力，并被用作递送DNA或蛋白质的通用载体。用硫酸乙酰肝素（HS）寡糖对假病毒颗粒进行冷冻电镜重建，结果显示RGD环上有一个额外密度。设计了一组突变体来研究RGD序列（RGE突变体）和位于其下游的一个碱性序列各自的作用。结果表明，RGE突变体与缺乏HS的CHO - 2241细胞的结合被消除，并且出乎意料的是，碱性序列的突变（从KQKR变为AQAS）显著降低了病毒假颗粒对整合素的识别。因此，这个碱性序列参与整合素对接，表明HSPGs和整合素受体之间存在密切的相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/924b/2833306/5a9095000006/JBB2010-541939.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/924b/2833306/9e29f13c7681/JBB2010-541939.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/924b/2833306/d197eea94294/JBB2010-541939.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/924b/2833306/f6dec0e3118c/JBB2010-541939.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/924b/2833306/5a9095000006/JBB2010-541939.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/924b/2833306/9e29f13c7681/JBB2010-541939.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/924b/2833306/d197eea94294/JBB2010-541939.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/924b/2833306/f6dec0e3118c/JBB2010-541939.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/924b/2833306/5a9095000006/JBB2010-541939.004.jpg

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