Structural and functional protein network analyses predict novel signaling functions for rhodopsin

Christina Kiel, Andreas Vogt, Anne Campagna, Andrew Chatr-Aryamontri, Magdalena Swiatek-De Lange, Monika Beer, Sylvia Bolz, Andreas F. MacK, Norbert Kinkl, Gianni Cesareni, Luis Serrano, Marius Ueffing

Research output: Contribution to journalArticle

Abstract

Orchestration of signaling, photoreceptor structural integrity, and maintenance needed for mammalian vision remain enigmatic. By integrating three proteomic data sets, literature mining, computational analyses, and structural information, we have generated a multiscale signal transduction network linked to the visual G protein-coupled receptor (GPCR) rhodopsin, the major protein component of rod outer segments. This network was complemented by domain decomposition of protein-protein interactions and then qualified for mutually exclusive or mutually compatible interactions and ternary complex formation using structural data. The resulting information not only offers a comprehensive view of signal transduction induced by this GPCR but also suggests novel signaling routes to cytoskeleton dynamics and vesicular trafficking, predicting an important level of regulation through small GTPases. Further, it demonstrates a specific disease susceptibility of the core visual pathway due to the uniqueness of its components present mainly in the eye. As a comprehensive multiscale network, it can serve as a basis to elucidate the physiological principles of photoreceptor function, identify potential disease-associated genes and proteins, and guide the development of therapies that target specific branches of the signaling pathway.

Original languageEnglish
Article number551
JournalMolecular Systems Biology
Volume7
DOIs
Publication statusPublished - 2011

Keywords

  • protein interaction network
  • rhodopsin signaling
  • structural modeling

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Computational Theory and Mathematics
  • Information Systems
  • Applied Mathematics

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    Kiel, C., Vogt, A., Campagna, A., Chatr-Aryamontri, A., Swiatek-De Lange, M., Beer, M., Bolz, S., MacK, A. F., Kinkl, N., Cesareni, G., Serrano, L., & Ueffing, M. (2011). Structural and functional protein network analyses predict novel signaling functions for rhodopsin. Molecular Systems Biology, 7, [551]. https://doi.org/10.1038/msb.2011.83