CaltechAUTHORS
  A Caltech Library Service

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

Wojtowicz, Woj M. and Vielmetter, Jost and Fernandes, Ricardo A. and Siepe, Dirk H. and Eastman, Catharine L. and Chisholm, Gregory B. and Cox, Sarah and Klock, Heath and Anderson, Paul W. and Rue, Sarah M. and Miller, Jessica J. and Glaser, Scott M. and Bragstad, Melisa L. and Vance, Julie and Lam, Annie W. and Lesley, Scott A. and Zinn, Kai and Garcia, K. Christopher (2020) A Human IgSF Cell-Surface Interactome Reveals a Complex Network of Protein-Protein Interactions. Cell, 182 (4). pp. 1027-1043. ISSN 0092-8674. PMCID PMC7440162. https://resolver.caltech.edu/CaltechAUTHORS:20200821-110146006

[img]
Preview
PDF (Free Elsevier COVID-19 resource) - Published Version
See Usage Policy.

10Mb
[img] MS Word (Data S1) - Supplemental Material
See Usage Policy.

437Kb
[img] MS Excel (Data S2) - Supplemental Material
See Usage Policy.

3346Kb
[img] MS Excel (Data S3) - Supplemental Material
See Usage Policy.

47Kb
[img] MS Excel (Data S4) - Supplemental Material
See Usage Policy.

157Kb
[img] MS Excel (Data S5) - Supplemental Material
See Usage Policy.

21Kb

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20200821-110146006

Abstract

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.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.cell.2020.07.025DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7440162PubMed CentralArticle
ORCID:
AuthorORCID
Vielmetter, Jost0000-0002-4314-7163
Zinn, Kai0000-0002-6706-5605
Garcia, K. Christopher0000-0001-9273-0278
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.
Funders:
Funding AgencyGrant Number
Sean ParkerUNSPECIFIED
Parker FoundationUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
G. Harold and Leila Y. Mathers Charitable FoundationUNSPECIFIED
NIHR37 NS28182
Caltech Beckman InstituteUNSPECIFIED
Issue or Number:4
PubMed Central ID:PMC7440162
Record Number:CaltechAUTHORS:20200821-110146006
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200821-110146006
Official Citation:Woj M. Wojtowicz, Jost Vielmetter, Ricardo A. Fernandes, Dirk H. Siepe, Catharine L. Eastman, Gregory B. Chisholm, Sarah Cox, Heath Klock, Paul W. Anderson, Sarah M. Rue, Jessica J. Miller, Scott M. Glaser, Melisa L. Bragstad, Julie Vance, Annie W. Lam, Scott A. Lesley, Kai Zinn, K. Christopher Garcia, A Human IgSF Cell-Surface Interactome Reveals a Complex Network of Protein-Protein Interactions, Cell, Volume 182, Issue 4, 2020, Pages 1027-1043.e17, ISSN 0092-8674, https://doi.org/10.1016/j.cell.2020.07.025. (http://www.sciencedirect.com/science/article/pii/S0092867420309338)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:105060
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:21 Aug 2020 19:42
Last Modified:24 Aug 2020 16:14

Repository Staff Only: item control page