Pathogen receptor discovery with a microfluidic human membrane protein array

Autor: Gregory Neveu, Michal Pellach, Yair Glick, Ariella Oppenheim, Ya'ara Ben-Ari, Jim Boonyaratanakornkit, Nir Drayman, Doron Gerber, Dorit Avrahami, Shirit Einav
Rok vydání: 2016
Předmět:
Zdroj: Proceedings of the National Academy of Sciences
ISSN: 1091-6490
0027-8424
DOI: 10.1073/pnas.1518698113
Popis: 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.
Databáze: OpenAIRE