Glick Yair, Ben-Ari Ya'ara, Drayman Nir, Pellach Michal, Neveu Gregory, Boonyaratanakornkit Jim, Avrahami Dorit, Einav Shirit, Oppenheim Ariella, Gerber Doron
Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, 5290002, Israel;
Faculty of Medicine, Hebrew University, Jerusalem, 9112001, Israel;
Proc Natl Acad Sci U S A. 2016 Apr 19;113(16):4344-9. doi: 10.1073/pnas.1518698113. Epub 2016 Apr 4.
The discovery of how a pathogen invades a cell requires one to determine which host cell receptors are exploited. This determination is a challenging problem because the receptor is invariably a membrane protein, which represents an Achilles heel in proteomics. We have developed a universal platform for high-throughput expression and interaction studies of membrane proteins by creating a microfluidic-based comprehensive human membrane protein array (MPA). The MPA is, to our knowledge, the first of its kind and offers a powerful alternative to conventional proteomics by enabling the simultaneous study of 2,100 membrane proteins. We characterized direct interactions of a whole nonenveloped virus (simian virus 40), as well as those of the hepatitis delta enveloped virus large form antigen, with candidate host receptors expressed on the MPA. Selected newly discovered membrane protein-pathogen interactions were validated by conventional methods, demonstrating that the MPA is an important tool for cellular receptor discovery and for understanding pathogen tropism.
病原体如何侵入细胞这一发现需要确定其利用了哪些宿主细胞受体。这一确定过程颇具挑战性，因为受体通常是膜蛋白，而膜蛋白是蛋白质组学中的薄弱环节。我们通过创建基于微流控的综合性人类膜蛋白阵列（MPA），开发了一个用于膜蛋白高通量表达和相互作用研究的通用平台。据我们所知，MPA是同类中的首个产品，通过能够同时研究2100种膜蛋白，为传统蛋白质组学提供了强大的替代方法。我们表征了整个无包膜病毒（猴病毒40）以及丁型肝炎包膜病毒大表面抗原与MPA上表达的候选宿主受体的直接相互作用。通过传统方法验证了选定的新发现的膜蛋白-病原体相互作用，表明MPA是细胞受体发现和理解病原体嗜性的重要工具。
