9EW2
High resolution structure of FZD7 in complex with miniGs protein
Summary for 9EW2
| Entry DOI | 10.2210/pdb9ew2/pdb |
| Related | 9EPO |
| EMDB information | 19881 31340 |
| Descriptor | GNAS complex locus,Isoform 4 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Ggamma, ... (5 entities in total) |
| Functional Keywords | gpcpr, frizzled, fzd7, membrane protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 5 |
| Total formula weight | 159883.17 |
| Authors | Bous, J.,Kinsolving, J.,Gratz, L.,Scharf, M.M.,Voss, J.,Selcuk, B.,Adebali, O.,Schulte, G. (deposition date: 2024-04-03, release date: 2024-10-02, Last modification date: 2025-04-09) |
| Primary citation | Bous, J.,Kinsolving, J.,Gratz, L.,Scharf, M.M.,Voss, J.H.,Selcuk, B.,Adebali, O.,Schulte, G. Structural basis of frizzled 7 activation and allosteric regulation. Nat Commun, 15:7422-7422, 2024 Cited by PubMed Abstract: Frizzleds (ten paralogs: FZD) belong to the class F of G protein-coupled receptors (GPCRs), which remains poorly understood despite its crucial role in multiple key biological functions including embryonic development, stem cell regulation, and homeostasis in the adult. FZD, one of the most studied members of the family, is more specifically involved in the migration of mesendoderm cells during the development and renewal of intestinal stem cells in adults. Moreover, FZD has been highlighted for its involvement in tumor development predominantly in the gastrointestinal tract. This study reports the structure of inactive FZD, without any stabilizing mutations, determined by cryo-electron microscopy (cryo-EM) at 1.9 Å resolution. We characterize a fluctuating water pocket in the core of the receptor important for FZD dynamics. Molecular dynamics simulations are used to investigate the temporal distribution of those water molecules and their importance for potential conformational changes in FZD. Moreover, we identify lipids interacting with the receptor core and a conserved cholesterol-binding site, which displays a key role in FZD association with a transducer protein, Disheveled (DVL), and initiation of downstream signaling and signalosome formation. PubMed: 39198452DOI: 10.1038/s41467-024-51664-4 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.2 Å) |
Structure validation
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