Signal proteins

Signal protein page

The selection page allows users to find a signal protein or family (grouped in the 4 main G protein families) by searching or browsing.

The browser displays a hierarchical view of the families, and the proteins in each family. Selecting either a receptor or family will take you to the corresponding receptor/family page. Species orthologs can be selected when toggleing the Species button to ‘All’

The page displays basic information about the selected protein and a sequence viewer a snake-like diagrams. The diagrams can be colored by properties, receptor interface and barcode information.

GPCR-G protein coupling

The page shows statistics on known coupling preferences as extracted from Guide to PHARMACOLOGY as:

  1. an interactive Venn diagram, which highlights the number of reported receptors for each G protein coupling combination
  2. an interactive phylogenetic tree, for which concentric circles illustrate the G protein-coupling selectivity of each GPCR the four dots depict both primary and secondary G protein coupling (from inside to outside: Gαs, Gαi/o, Gαq/11, Gα12/13). Tree nodes can be highlighted and selected to retrieve clade-specific receptor sets, which can be used in dedicated segment specific sequence alignments.

Highlighting and selection of receptors populates a field, which can be used as an input for dedicated segment spewcific sequence alignments.

G protein alignments

The “Structure-based alignments” tool allows for alignment of user selected G proteins and sequence segments. Using the tool is a two step process.

  1. The user is first presented with a G protein selection page.
  2. The user is presented with a sequence segment selection page. The user can select one or more sequence segments, and/or expand each segment to select the residues within it individually.

After completing these two steps, an alignment is displayed. To display the sequence number of an aligned residue, as well as generic numbers (CGN numbering), hover the mouse over it. At the bottom of the page, a consensus sequence as well as conservation statistics for amino acids and chemical features are displayed.

Interface mapping

Maps the β2-Gαs complex (PDB: 3SN6) interaction interface onto a snake plot of a selected receptor and highlights conserved and accessible interactions.

  • Flock, T., Hauser, A. S., Lund, N., Gloriam, D. E., Balaji, S., & Babu, M. M., “Selectivity determinants of GPCR–G-protein binding.”, 2017, Nature, May 18;545(7654):317-322 10.1038/nature22070