Structural and functional protein network analyses predict novel signaling functions for rhodopsin
Open Access
- 1 January 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Molecular Systems Biology
- Vol. 7 (1), 551
- https://doi.org/10.1038/msb.2011.83
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.Keywords
This publication has 94 references indexed in Scilit:
- Hippocalcin, new Ca2+ sensor of a ROS-GC subfamily member, ONE-GC, membrane guanylate cyclase transduction systemMolecular and Cellular Biochemistry, 2009
- Ciliary targeting motif VxPx directs assembly of a trafficking module through Arf4The EMBO Journal, 2009
- Tissue specificity and the human protein interaction networkMolecular Systems Biology, 2009
- Signal transducing membrane complexes of photoreceptor outer segmentsVision Research, 2008
- Membrane identity and GTPase cascades regulated by toggle and cut‐out switchesMolecular Systems Biology, 2008
- Proteome survey reveals modularity of the yeast cell machineryNature, 2006
- Towards a proteome-scale map of the human protein–protein interaction networkNature, 2005
- Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometryNature, 2002
- Functional organization of the yeast proteome by systematic analysis of protein complexesNature, 2002
- A comprehensive two-hybrid analysis to explore the yeast protein interactomeProceedings of the National Academy of Sciences, 2001