Identification of a Putative Intracellular Allosteric Antagonist Binding-Site in the CXC Chemokine Receptors 1 and 2

2008 ◽  
Vol 74 (5) ◽  
pp. 1193-1202 ◽  
Author(s):  
David J. Nicholls ◽  
Nick P. Tomkinson ◽  
Katherine E. Wiley ◽  
Anne Brammall ◽  
Lorna Bowers ◽  
...  
Keyword(s):  
Binding Site ◽  
Chemokine Receptors ◽  
Cxc Chemokine ◽  
Antagonist Binding

Discovery and Mapping of an Intracellular Antagonist Binding Site at the Chemokine Receptor CCR2

2014 ◽  
Vol 86 (4) ◽  
pp. 358-368 ◽  
Author(s):  
Annelien J.M. Zweemer ◽  
Julia Bunnik ◽  
Margo Veenhuizen ◽  
Fabiana Miraglia ◽  
Eelke B. Lenselink ◽  
...  
Keyword(s):  
Binding Site ◽  
Chemokine Receptor ◽  
Antagonist Binding ◽  
Chemokine Receptor Ccr2

scholarly journals Evolution of chemokine receptors is driven by mutations in the sodium binding site

2018 ◽  
Vol 14 (6) ◽  
pp. e1006209 ◽  
Author(s):  
Bruck Taddese ◽  
Madeline Deniaud ◽  
Antoine Garnier ◽  
Asma Tiss ◽  
Hajer Guissouma ◽  
...  
Keyword(s):  
Binding Site ◽  
Chemokine Receptors ◽  
Sodium Binding

Down-regulation of neutrophil functions by the ELR+CXC chemokine platelet basic protein

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 2965-2972 ◽  
Author(s):  
Jan E. Ehlert ◽  
Andreas Ludwig ◽  
Tobias A. Grimm ◽  
Buko Lindner ◽  
Hans-Dieter Flad ◽  
...  
Keyword(s):  
Amino Acids ◽  
Binding Sites ◽  
Chemokine Receptors ◽  
Cell Activation ◽  
Basic Protein ◽  
Cathepsin G ◽  
Terminal Part ◽  
Down Regulation ◽  
Cxc Chemokine ◽  
Continuous Accumulation

Abstract The platelet-derived neutrophil-activating peptide 2 (NAP-2, 70 amino acids) belongs to the ELR+ CXC subfamily of chemokines. Similar to other members of this group, such as IL-8, NAP-2 activates chemotaxis and degranulation in neutrophils (polymorphonuclear [PMN]) through chemokine receptors CXCR-1 and CXCR-2. However, platelets do not secrete NAP-2 as an active chemokine but as the C-terminal part of several precursors that lack PMN-stimulating capacity. As we have previously shown, PMN themselves may liberate NAP-2 from the precursor connective tissue-activating peptide III (CTAP-III, 85 amino acids) by proteolysis. Instead of inducing cell activation, continuous accumulation of the chemokine in the surroundings of the processing cells results in the down-regulation of specific surface-expressed NAP-2 binding sites and in the desensitization of chemokine-induced PMN degranulation. Thus, NAP-2 precursors may be regarded as indirect mediators of functional desensitization in neutrophils. In the current study we investigated the biologic impact of another major NAP-2 precursor, the platelet basic protein (PBP, 94 amino acids). We show that PBP is considerably more potent than CTAP-III to desensitize degranulation and chemotaxis in neutrophils. We present data suggesting that the high desensitizing capacity of PBP is based on its enhanced proteolytic cleavage into NAP-2 by neutrophil-expressed cathepsin G and that it involves efficient down-regulation of surface-expressed CXCR-2 while CXCR-1 is hardly affected. Correspondingly, we found PBP and, less potently, CTAP-III to inhibit CXCR-2– but not CXCR-1– dependent chemotaxis of neutrophils toward NAP-2. Altogether our findings demonstrate that the anti-inflammatory capacity of NAP-2 is governed by the species of its precursors.

scholarly journals Specific IK29 (novel α1-adrenoceptor antagonist) binding site in rabbit prostate and aorta

1992 ◽  
Vol 58 ◽  
pp. 173
Author(s):  
Tomohiro Yamaguchi ◽  
Toshihiko Tsujii ◽  
Shigeru Ito ◽  
Hiroshi Azuma
Keyword(s):  
Binding Site ◽  
Adrenoceptor Antagonist ◽  
Antagonist Binding

scholarly journals Human Immunodeficiency Virus-1 Entry Into Purified Blood Dendritic Cells Through CC and CXC Chemokine Coreceptors

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1379-1386 ◽  
Author(s):  
Seyoum Ayehunie ◽  
Eduardo A. Garcia-Zepeda ◽  
James A. Hoxie ◽  
Richard Horuk ◽  
Thomas S. Kupper ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dendritic Cells ◽  
Chemokine Receptor ◽  
Chemokine Receptors ◽  
Monocyte Chemoattractant Protein 1 ◽  
Rna Transcripts ◽  
Inflammatory Protein ◽  
Immunodeficiency Virus ◽  
Cxc Chemokine ◽  
Cc Chemokines

Abstract Blood dendritic cells (DC) are susceptible to both macrophage (M) and T-cell line (T) tropic human immunodeficiency virus type 1. The CC chemokines RANTES, macrophage inflammatory protein-1α (MIP-1α), MIP-1β, eotaxin, and, to a lesser extent, monocyte chemoattractant protein-1 (MCP-1) and MCP-4 blocked entry of M-tropic virus into blood DC. The CXC chemokine, SDF-1, a fusin (CXCR4 chemokine receptor) ligand, and an antifusin antibody inhibited DC entry by T-tropic virus. Purified blood DC contained CCR1, CCR2, CCR3, and CCR5 as well as the CXCR4 chemokine receptor RNA transcripts and high levels of fusin on the cell surface. The coexpression of multiple chemokine receptors offers a molecular mechanism to explain the permissiveness of DC for both M- and T-tropic viruses.

scholarly journals Mutational Analysis of the Antagonist-binding Site of the Histamine H1Receptor

1999 ◽  
Vol 274 (42) ◽  
pp. 29994-30000 ◽  
Author(s):  
Kerstin Wieland ◽  
Anton M. Ter Laak ◽  
Martine J. Smit ◽  
Ronald Kühne ◽  
Henk Timmerman ◽  
...  
Keyword(s):  
Binding Site ◽  
Mutational Analysis ◽  
Antagonist Binding
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