RT info:eu-repo/semantics/article
T1 Role of the second extracellular loop of human C3a receptor in agonist binding and receptor function
A1 Chao, Ta-Hsiang
A1 Ember, Julia A.
A1 Wang, Meiying
A1 Bayón Prieto, Yolanda
A1 Hugli, Tony E.
A1 Ye, Richard D.
K1 Calcio
K1 Receptor C3a humano
K1 Human C3a receptorin
K1 24 Ciencias de la Vida
AB 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.
PB Elsevier
SN 0021-9258
YR 1999
FD 1999
LK https://uvadoc.uva.es/handle/10324/47501
UL https://uvadoc.uva.es/handle/10324/47501
LA eng
NO Journal of Biological Chemistry, 1999, vol. 274, n. 14, p. 9721-9728
NO Producción Científica
DS UVaDOC
RD 11-jul-2024