2026-07-22T20:11:53Zhttps://uvadoc.uva.es/oai/request

oai:uvadoc.uva.es:10324/475012022-07-18T09:33:04Zcom_10324_32522com_10324_952com_10324_894col_10324_32523

Chao, Ta-Hsiang Ember, Julia A. Wang, Meiying Bayón Prieto, Yolanda Hugli, Tony E. Ye, Richard D. 2021-07-19T06:09:55Z 2021-07-19T06:09:55Z 1999 Journal of Biological Chemistry, 1999, vol. 274, n. 14, p. 9721-9728 0021-9258 https://uvadoc.uva.es/handle/10324/47501 10.1074/jbc.274.14.9721 9721 14 9728 Journal of Biological Chemistry 274 Producción Científica The C3a anaphylatoxin receptor (C3aR) is a G protein-coupled receptor with an unusually large second extra-cellular loop (e2 loop,;172 amino acids). To determinethe function of this unique structure, chimeric and de-letion mutants were prepared and analyzed in trans-fected RBL-2H3 cells. Whereas replacement of the C3aRN-terminal segment with that from the human C5a re-ceptor had minimal effect on C3a binding, substitutionof the e2 loop with a smaller e2 loop from the C5a recep-tor (C5aR) abolished binding of125I-C3a and C3a-stimu-lated calcium mobilization. However, as much as 65% ofthe e2 loop sequence (amino acids 198 –308) may be re-moved without affecting C3a binding or calcium re-sponses. The e2 loop sequences adjacent to the trans-membrane domains contain multiple aspartate residuesand are found to play an important role in C3a bindingbased on deletion mutagenesis. Replacement of five as-partate residues in the e2 loop with lysyl residues sig-nificantly compromised both the binding and functionalcapabilities of the C3a receptor mediated by intact C3aor by two C3a analog peptides. These data suggest atwo-site C3a-C3aR interaction model similar to that es-tablished for C5a/C5aR. The anionic residues near the Nand C termini of the C3aR e2 loop constitute a non-effector secondary interaction site with cationic resi-dues in the C-terminal helical region of C3a, whereas theC3a C-terminal sequence LGLAR engages the primaryeffector site in C3aR. application/pdf eng Elsevier info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/4.0/ © Elsevier Attribution-NonCommercial-NoDerivatives 4.0 Internacional Calcio Receptor C3a humano Human C3a receptorin 24 Ciencias de la Vida Role of the second extracellular loop of human C3a receptor in agonist binding and receptor function info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion https://www.sciencedirect.com/science/article/pii/S002192581987309X SI