The role of the N-terminal domain of the complement fragment receptor C5L2 in ligand binding

Scola, A. M., Higginbottom, A., Partridge, L, J., Reid, R. C., Woodruff, T., Taylor, S. M., Fairlie, D. P. and Monk, P. N. (2007) The role of the N-terminal domain of the complement fragment receptor C5L2 in ligand binding. Journal of Biological Chemistry, 282 6: 3664-3671. doi:10.1074/jbc.M609178200

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ128052_OA.pdf Full text (open access) application/pdf 498.53KB 0

Author Scola, A. M.
Higginbottom, A.
Partridge, L, J.
Reid, R. C.
Woodruff, T.
Taylor, S. M.
Fairlie, D. P.
Monk, P. N.
Title The role of the N-terminal domain of the complement fragment receptor C5L2 in ligand binding
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2007
Sub-type Article (original research)
DOI 10.1074/jbc.M609178200
Open Access Status File (Publisher version)
Volume 282
Issue 6
Start page 3664
End page 3671
Total pages 8
Editor H. Tabor
Place of publication Bethesda, M.D, U.S.A.
Publisher American Society for Biochemistry Molecular Biology
Collection year 2008
Language eng
Subject C1
320599 Pharmacology not elsewhere classified
730102 Immune system and allergy
780103 Chemical sciences
320305 Medical Biochemistry - Proteins and Peptides
Abstract C5L2 is a new cellular receptor found to interact with the human anaphylatoxins complement factor C5a and its C-terminal cleavage product C5a des Arg. The classical human C5a receptor (CSaR) preferentially binds C5a, with a 10-100-fold lower affinity for C5a des Arg. In contrast, C5L2 binds both ligands with nearly equal affinity. C5aR presents acidic and tyrosine residues in its N terminus that interact with the core of C5a while a hydrophobic pocket formed by the transmembrane helices interacts with residues in the C terminus of C5a. Here, we have investigated the molecular basis for the increased affinity of C5L2 for C5a des Arg. Rat and mouse C5L2 preferentially bound C5a des Arg, whereas rodent C5aR showed much higher affinity for intact C5a. Effective peptidic and non-peptidic ligands for the transmembrane hydrophobic pocket of C5aR were poor inhibitors of ligand binding to C5L2. An antibody raised against the N terminus of human C5L2 did not affect the binding of C5a to C5L2 but did inhibit C5a des Arg binding. A chimeric C5L2, containing the N terminus of C5aR, had little effect on the affinity for C5a des Arg. Mutation of acidic and tyrosine residues in the N terminus of human C5L2 revealed that 3 residues were critical for C5a des Arg binding but had little involvement in C5a binding. C5L2 thus appears to bind C5a and C5a des Arg by different mechanisms, and, unlike C5aR, C5L2 uses critical residues in its N-terminal domain for binding only to C5a des Arg.
Keyword Biochemistry & Molecular Biology
Human C5a Receptor
Human C3a Receptor
Q-Index Code C1
Q-Index Status Confirmed Code

Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 26 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 28 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 18 Feb 2008, 16:24:44 EST