7c6a
Crystal structure of AT2R-BRIL and SRP2070_Fab complexCrystal structure of AT2R-BRIL and SRP2070_Fab complex
Structural highlights
DiseaseAGTR2_HUMAN X-linked non-syndromic intellectual disability. FunctionC562_ECOLX Electron-transport protein of unknown function.AGTR2_HUMAN Receptor for angiotensin II. Cooperates with MTUS1 to inhibit ERK2 activation and cell proliferation.[1] Publication Abstract from PubMedG-protein-coupled receptors (GPCRs)-the largest family of cell-surface membrane proteins-mediate the intracellular signal transduction of many external ligands. Thus, GPCRs have become important drug targets. X-ray crystal structures of GPCRs are very useful for structure-based drug design (SBDD). Herein, we produced a new antibody (SRP2070) targeting the thermostabilised apocytochrome b562 from Escherichia coli M7W/H102I/R106L (BRIL). We found that a fragment of this antibody (SRP2070Fab) facilitated the crystallisation of the BRIL-tagged, ligand bound GPCRs, 5HT(1B) and AT(2)R. Furthermore, the electron densities of the ligands were resolved, suggesting that SPR2070Fab is versatile and adaptable for GPCR SBDD. We anticipate that this new tool will significantly accelerate structure determination of other GPCRs and the design of small molecular drugs targeting them. The discovery of a new antibody for BRIL-fused GPCR structure determination.,Miyagi H, Asada H, Suzuki M, Takahashi Y, Yasunaga M, Suno C, Iwata S, Saito JI Sci Rep. 2020 Jul 15;10(1):11669. doi: 10.1038/s41598-020-68355-x. PMID:32669569[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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