Matches in SemOpenAlex for { <https://semopenalex.org/work/W4281744037> ?p ?o ?g. }
- W4281744037 abstract "Abstract Chemokine receptors constitute an important subfamily of G protein-coupled receptors (GPCRs), and they are critically involved in a broad range of immune response mechanisms. Ligand promiscuity among these receptors makes them an interesting target to explore novel aspects of biased agonism. Here, we comprehensively characterize two chemokine receptors namely, CXCR4 and CXCR7, which share a common chemokine agonist (CXCL12), in terms of their G-protein coupling, β-arrestin (βarr) recruitment, contribution of GRKs, and ERK1/2 MAP kinase activation. We observe that CXCR7 lacks G-protein coupling while maintaining robust βarr recruitment with a major contribution of GRK5/6. On the other hand, CXCR4 displays robust G-protein activation as expected, however, it exhibits significantly reduced βarr-coupling compared to CXCR7 in response to their shared natural agonist, CXCL12. These two receptors induce distinct βarr conformations even when activated by the same agonist, and CXCR7, unlike CXCR4, fails to activate ERK1/2 MAP kinase. We further determine the crystal structure of βarr2 in complex with a carboxyl-terminal phosphopeptide derived from CXCR7, which reveals a smaller interdomain rotation than observed previously for activated βarrs. Importantly, structure-guided cellular experiments reveal a key contribution of a single phosphorylation site in CXCR7 on βarr recruitment and endosomal trafficking. Taken together, our study provides molecular insights into intrinsic bias encoded in the CXCR4-CXCR7 system, and it has broad implications for therapeutically important framework of biased agonism." @default.
- W4281744037 created "2022-06-13" @default.
- W4281744037 creator A5002744498 @default.
- W4281744037 creator A5008919130 @default.
- W4281744037 creator A5012484540 @default.
- W4281744037 creator A5015419181 @default.
- W4281744037 creator A5021724487 @default.
- W4281744037 creator A5028192154 @default.
- W4281744037 creator A5028462736 @default.
- W4281744037 creator A5043274215 @default.
- W4281744037 creator A5043721830 @default.
- W4281744037 creator A5047792171 @default.
- W4281744037 creator A5049054862 @default.
- W4281744037 creator A5049768801 @default.
- W4281744037 creator A5051460873 @default.
- W4281744037 creator A5055127190 @default.
- W4281744037 creator A5059771748 @default.
- W4281744037 creator A5061332928 @default.
- W4281744037 creator A5064405661 @default.
- W4281744037 creator A5064890126 @default.
- W4281744037 creator A5064921157 @default.
- W4281744037 creator A5075984445 @default.
- W4281744037 creator A5079844419 @default.
- W4281744037 creator A5079977466 @default.
- W4281744037 creator A5080849554 @default.
- W4281744037 creator A5082061805 @default.
- W4281744037 creator A5083251665 @default.
- W4281744037 creator A5086493890 @default.
- W4281744037 creator A5090122866 @default.
- W4281744037 creator A5091565573 @default.
- W4281744037 date "2022-06-07" @default.
- W4281744037 modified "2023-10-08" @default.
- W4281744037 title "Molecular insights into intrinsic transducer-coupling bias in the CXCR4-CXCR7 system" @default.
- W4281744037 cites W1971126800 @default.
- W4281744037 cites W1977091420 @default.
- W4281744037 cites W1984462878 @default.
- W4281744037 cites W1987000399 @default.
- W4281744037 cites W1994342014 @default.
- W4281744037 cites W1995656788 @default.
- W4281744037 cites W2013971421 @default.
- W4281744037 cites W2015198542 @default.
- W4281744037 cites W2018506708 @default.
- W4281744037 cites W2019879894 @default.
- W4281744037 cites W2036251618 @default.
- W4281744037 cites W2057771278 @default.
- W4281744037 cites W2074814327 @default.
- W4281744037 cites W2077936290 @default.
- W4281744037 cites W2086617442 @default.
- W4281744037 cites W2114636625 @default.
- W4281744037 cites W2144081223 @default.
- W4281744037 cites W2151453636 @default.
- W4281744037 cites W2153044787 @default.
- W4281744037 cites W2153960708 @default.
- W4281744037 cites W2163341755 @default.
- W4281744037 cites W2168193216 @default.
- W4281744037 cites W218010454 @default.
- W4281744037 cites W2180229411 @default.
- W4281744037 cites W2260167160 @default.
- W4281744037 cites W2302828574 @default.
- W4281744037 cites W2303462194 @default.
- W4281744037 cites W2597463553 @default.
- W4281744037 cites W2739933313 @default.
- W4281744037 cites W2755818053 @default.
- W4281744037 cites W2767610564 @default.
- W4281744037 cites W2790057789 @default.
- W4281744037 cites W2797069917 @default.
- W4281744037 cites W2901194852 @default.
- W4281744037 cites W2901881106 @default.
- W4281744037 cites W2918548579 @default.
- W4281744037 cites W2946861851 @default.
- W4281744037 cites W2976162059 @default.
- W4281744037 cites W2999487242 @default.
- W4281744037 cites W3000145087 @default.
- W4281744037 cites W3035794825 @default.
- W4281744037 cites W3038566978 @default.
- W4281744037 cites W3044480534 @default.
- W4281744037 cites W3085560188 @default.
- W4281744037 cites W3107666328 @default.
- W4281744037 cites W3111751350 @default.
- W4281744037 cites W3133800414 @default.
- W4281744037 cites W3156609721 @default.
- W4281744037 cites W3203078114 @default.
- W4281744037 cites W4210440837 @default.
- W4281744037 doi "https://doi.org/10.1101/2022.06.06.494935" @default.
- W4281744037 hasPublicationYear "2022" @default.
- W4281744037 type Work @default.
- W4281744037 citedByCount "4" @default.
- W4281744037 countsByYear W42817440372023 @default.
- W4281744037 crossrefType "posted-content" @default.
- W4281744037 hasAuthorship W4281744037A5002744498 @default.
- W4281744037 hasAuthorship W4281744037A5008919130 @default.
- W4281744037 hasAuthorship W4281744037A5012484540 @default.
- W4281744037 hasAuthorship W4281744037A5015419181 @default.
- W4281744037 hasAuthorship W4281744037A5021724487 @default.
- W4281744037 hasAuthorship W4281744037A5028192154 @default.
- W4281744037 hasAuthorship W4281744037A5028462736 @default.
- W4281744037 hasAuthorship W4281744037A5043274215 @default.
- W4281744037 hasAuthorship W4281744037A5043721830 @default.
- W4281744037 hasAuthorship W4281744037A5047792171 @default.
- W4281744037 hasAuthorship W4281744037A5049054862 @default.