TY - JOUR
T1 - Pathogen receptor discovery with a microfluidic human membrane protein array
AU - Glick, Yair
AU - Ben-Ari, Ya'ara
AU - Drayman, Nir
AU - Pellach, Michal
AU - Neveu, Gregory
AU - Boonyaratanakornkit, Jim
AU - Avrahami, Dorit
AU - Einav, Shirit
AU - Oppenheim, Ariella
AU - Gerber, Doron
N1 - Funding Information: This work was supported by European Research Council Starter Grant 309600 (to D.G.); Israel Science Foundation Grant 715/11 (to D.G.) and Israel Science Foundation Grant 291/12 (to A.O.); American Cancer Society Grant RSG-14-11 0-0 1-MPC (to S.E.); Doris Duke Charitable Foundation Grant 2013100 (to S.E.). G.N. was supported by Child Health Research Institute, Lucile Packard Foundation for Children's Health, and Stanford Clinical and Translational Science Award Grant UL1 TR000093.
PY - 2016/4/19
Y1 - 2016/4/19
N2 - 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 ofmembrane 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.
AB - 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 ofmembrane 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.
KW - Integrated microfluidics
KW - Membrane protein array
KW - Pathogen-host interactions
KW - Receptor discovery
UR - http://www.scopus.com/inward/record.url?scp=84964238224&partnerID=8YFLogxK
U2 - 10.1073/pnas.1518698113
DO - 10.1073/pnas.1518698113
M3 - مقالة
C2 - 27044079
SN - 0027-8424
VL - 113
SP - 4344
EP - 4349
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 16
ER -
