UM
Role of the second extracellular loop of human C3a receptor in agonist binding and receptor function
Chao T.-H.4; Ember J.A.4; Wang M.4; Bayon Y.4; Hugli T.E.4; Ye R.D.4
1999-04-02
Source PublicationJournal of Biological Chemistry
ISSN00219258
Volume274Issue:14Pages:9721-9728
AbstractThe C3a anaphylatoxin receptor (C3aR) is a G protein-coupled receptor with an unusually large second extracellular loop (e2 loop, ~172 amino acids). To determine the function of this unique structure, chimeric and deletion mutants were prepared and analyzed in transfected RBL-2H3 cells. Whereas replacement of the C3aR N-terminal segment with that from the human C5a receptor had minimal effect on C3a binding, substitution of the e2 loop with a smaller e2 loop from the C5a receptor (C5aR) abolished binding of I-C3a and C3a-stimulated calcium mobilization. However, as much as 65% of the e2 loop sequence (amino acids 198-308) may be removed without affecting C3a binding or calcium responses. The e2 loop sequences adjacent to the transmembrane domains contain multiple aspartate residues and are found to play an important role in C3a binding based on deletion mutagenesis. Replacement of five aspartate residues in the e2 loop with lysyl residues significantly compromised both the binding and functional capabilities of the C3a receptor mediated by intact C3a or by two C3a analog peptides. These data suggest a two-site C3a-C3aR interaction model similar to that established for C5a/C5aR. The anionic residues near the N and C termini of the C3aR e2 loop constitute a non-effector secondary interaction site with cationic residues in the C-terminal helical region of C3a, whereas the C3a C-terminal sequence LGLAR engages the primary effector site in C3aR.
DOI10.1074/jbc.274.14.9721
URLView the original
Language英語
Fulltext Access
Citation statistics
Cited Times [WOS]:37   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Sidney Kimmel Cancer Center
2.CSIC-UVA - Instituto de Biologia y Genetica Molecular (IBGM)
3.University of Illinois at Chicago
4.Scripps Research Institute
Recommended Citation
GB/T 7714
Chao T.-H.,Ember J.A.,Wang M.,et al. Role of the second extracellular loop of human C3a receptor in agonist binding and receptor function[J]. Journal of Biological Chemistry,1999,274(14):9721-9728.
APA Chao T.-H.,Ember J.A.,Wang M.,Bayon Y.,Hugli T.E.,&Ye R.D..(1999).Role of the second extracellular loop of human C3a receptor in agonist binding and receptor function.Journal of Biological Chemistry,274(14),9721-9728.
MLA Chao T.-H.,et al."Role of the second extracellular loop of human C3a receptor in agonist binding and receptor function".Journal of Biological Chemistry 274.14(1999):9721-9728.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Chao T.-H.]'s Articles
[Ember J.A.]'s Articles
[Wang M.]'s Articles
Baidu academic
Similar articles in Baidu academic
[Chao T.-H.]'s Articles
[Ember J.A.]'s Articles
[Wang M.]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Chao T.-H.]'s Articles
[Ember J.A.]'s Articles
[Wang M.]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.