Welcome to the new version of CaltechAUTHORS. Login is currently restricted to library staff. If you notice any issues, please email coda@library.caltech.edu
Published August 20, 2020 | Supplemental Material + Published
Journal Article Open

A Human IgSF Cell-Surface Interactome Reveals a Complex Network of Protein-Protein Interactions


Cell-surface protein-protein interactions (PPIs) mediate cell-cell communication, recognition, and responses. We executed an interactome screen of 564 human cell-surface and secreted proteins, most of which are immunoglobulin superfamily (IgSF) proteins, using a high-throughput, automated ELISA-based screening platform employing a pooled-protein strategy to test all 318,096 PPI combinations. Screen results, augmented by phylogenetic homology analysis, revealed ∼380 previously unreported PPIs. We validated a subset using surface plasmon resonance and cell binding assays. Observed PPIs reveal a large and complex network of interactions both within and across biological systems. We identified new PPIs for receptors with well-characterized ligands and binding partners for "orphan" receptors. New PPIs include proteins expressed on multiple cell types and involved in diverse processes including immune and nervous system development and function, differentiation/proliferation, metabolism, vascularization, and reproduction. These PPIs provide a resource for further biological investigation into their functional relevance and may offer new therapeutic drug targets.

Additional Information

© 2020 Elsevier Inc. Received 14 February 2020, Revised 19 May 2020, Accepted 17 July 2020, Available online 20 August 2020. The authors thank Sean Parker and the Parker Foundation for a generous gift, the Howard Hughes Medical Institute (K.C.G.), the G. Harold and Leila Y. Mathers Charitable Foundation (K.C.G.), the National Institutes of Health (NIH R37 NS28182) (K.Z.), and the Caltech Beckman Institute (Caltech Protein Expression Center, J.V.) for support of this work. We thank Daisuke Hattori for help with data and statistical analyses. Author Contributions: Conceptualization, K.C.G., W.M.W., J.V., R.A.F., D.H.S., and K.Z.; Methodology, W.M.W., J.V., R.A.F., D.H.S., C.L.E., and P.W.A.; Software, J.V.; Validation, W.M.W., J.V., R.A.F., D.H.S., and C.L.E.; Formal Analysis, W.M.W., J.V., R.A.F., and D.H.S.; Investigation, W.M.W., J.V., R.A.F., D.H.S., C.L.E., G.B.C., S.C., H.K., P.W.A., S.M.R., J.J.M., M.L.B., J.V., and A.W.L.; Resources, J.V., S.A.L., S.C., H.K., and P.W.A.; Data Curation, D.H.S. and K.Z.; Writing – Original Draft, W.M.W. and J.V.; Writing – Review & Editing, K.C.G., W.M.W., J.V., R.A.F., D.H.S., C.L.E., and K.Z.; Visualization, W.M.W., J.V., R.A.F., D.H.S., and C.L.E.; Supervision, K.C.G., W.M.W., J.V., K.Z., S.A.L., S.C., P.W.A., and S.M.R.; Project Administration, K.C.G., W.M.W., J.V., S.A.L., and S.C.; Funding Acquisition, K.C.G. The authors declare no competing interests.

Attached Files

Published - Wojtowicz_2020p1027.pdf

Supplemental Material - 1-s2.0-S0092867420309338-mmc1.xlsx

Supplemental Material - 1-s2.0-S0092867420309338-mmc2.xlsx

Supplemental Material - 1-s2.0-S0092867420309338-mmc3.xlsx

Supplemental Material - 1-s2.0-S0092867420309338-mmc4.xlsx

Supplemental Material - 1-s2.0-S0092867420309338-mmc5.xlsx


Files (14.9 MB)
Name Size Download all
161.7 kB Download
447.9 kB Download
3.4 MB Download
49.1 kB Download
10.8 MB Preview Download
22.3 kB Download

Additional details

August 19, 2023
December 22, 2023