Front Immunol. 2018 Nov 26;9:2716. doi: 10.3389/fimmu.2018.02716. eCollection 2018.
Structural Immunology of Complement Receptors 3 and 4.
Frontiers in immunology
Thomas Vorup-Jensen, Rasmus Kjeldsen Jensen
Affiliations
Affiliations
- Biophysical Immunology Laboratory, Department of Biomedicine, Aarhus University, Aarhus, Denmark.
- Interdisciplinary Nanoscience Center, Aarhus University, Aarhus, Denmark.
- Department of Molecular Biology and Genetics-Structural Biology, Aarhus University, Aarhus, Denmark.
PMID: 30534123
PMCID: PMC6275225 DOI: 10.3389/fimmu.2018.02716
Abstract
Complement receptors (CR) 3 and 4 belong to the family of beta-2 (CD18) integrins. CR3 and CR4 are often co-expressed in the myeloid subsets of leukocytes, but they are also found in NK cells and activated T and B lymphocytes. The heterodimeric ectodomain undergoes considerable conformational change in order to switch the receptor from a structurally bent, ligand-binding in-active state into an extended, ligand-binding active state. CR3 binds the C3d fragment of C3 in a way permitting CR2 also to bind concomitantly. This enables a hand-over of complement-opsonized antigens from the cell surface of CR3-expressing macrophages to the CR2-expressing B lymphocytes, in consequence acting as an antigen presentation mechanism. As a more enigmatic part of their functions, both CR3 and CR4 bind several structurally unrelated proteins, engineered peptides, and glycosaminoglycans. No consensus motif in the proteinaceous ligands has been established. Yet, the experimental evidence clearly suggest that the ligands are primarily, if not entirely, recognized by a single site within the receptors, namely the metal-ion dependent adhesion site (MIDAS). Comparison of some recent identified ligands points to CR3 as inclined to bind positively charged species, while CR4, by contrast, binds strongly negative-charged species, in both cases with the critical involvement of deprotonated, acidic groups as ligands for the Mg
Keywords: cell adhesion; complement; complement receptors; divalent metal ions; drug repurposing; innate immunity; integrins; von willebrand facor A (VWA) domain
References
- J Biol Chem. 2007 Oct 19;282(42):30869-77 - PubMed
- J Cell Biol. 1988 Nov;107(5):1893-900 - PubMed
- Int J Mol Sci. 2012 Nov 09;13(11):14579-605 - PubMed
- Cell. 2002 Dec 27;111(7):927-30 - PubMed
- J Biol Chem. 2003 Sep 5;278(36):34395-402 - PubMed
- Exp Cell Res. 1992 Jun;200(2):242-52 - PubMed
- Stroke. 2007 Feb;38(2):303-7 - PubMed
- Nat Immunol. 2017 Aug;18(8):889-898 - PubMed
- J Biol Chem. 1994 Apr 1;269(13):10008-15 - PubMed
- Blood. 2006 May 1;107(9):3593-9 - PubMed
- Adv Exp Med Biol. 2008;632:23-33 - PubMed
- Int J Clin Pharmacol Ther. 2010 Nov;48(11):718-28 - PubMed
- J Nanopart Res. 2013 Aug 1;15(8):1874 - PubMed
- Proc Natl Acad Sci U S A. 1998 May 12;95(10):5490-4 - PubMed
- J Biol Chem. 1990 Jul 25;265(21):12119-22 - PubMed
- Cell Rep. 2015 Mar 11;:null - PubMed
- J Oncol Pharm Pract. 2012 Jun;18(2):264-70 - PubMed
- Circ Res. 2011 Nov 11;109(11):1199-201 - PubMed
- Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16737-41 - PubMed
- Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):16426-31 - PubMed
- Biochemistry. 2015 Feb 17;54(6):1408-20 - PubMed
- Adv Drug Deliv Rev. 2002 Oct 18;54(8):1145-55 - PubMed
- PLoS One. 2014 Nov 21;9(11):e112770 - PubMed
- Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10037-41 - PubMed
- Res Rep Biochem. 2016 Jul 7;2016(6):39-55 - PubMed
- Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):1873-8 - PubMed
- J Clin Invest. 1987 Aug;80(2):535-44 - PubMed
- Eur J Biochem. 2003 Apr;270(8):1710-23 - PubMed
- Blood. 2018 Jul 5;132(1):78-88 - PubMed
- Science. 1987 Sep 4;237(4819):1204-6 - PubMed
- Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10277-81 - PubMed
- Immunol Lett. 2017 Sep;189:73-81 - PubMed
- J Control Release. 2012 Jul 10;161(1):25-37 - PubMed
- Trends Immunol. 2016 Dec;37(12):844-854 - PubMed
- Arthritis Res Ther. 2014 Feb 04;16(1):R42 - PubMed
- Nature. 2008 May 1;453(7191):51-5 - PubMed
- Immunol Lett. 1987 Feb;14(3):183-90 - PubMed
- J Biol Chem. 2016 Aug 12;291(33):16963-76 - PubMed
- Adv Drug Deliv Rev. 2011 Sep 16;63(12):1008-19 - PubMed
- Biochemistry. 2005 Mar 22;44(11):4357-64 - PubMed
- Nat Nanotechnol. 2011 Jan;6(1):39-44 - PubMed
- J Immunol. 2011 Dec 15;187(12):6393-401 - PubMed
- J Bacteriol. 2004 Jun;186(11):3286-95 - PubMed
- Proc Natl Acad Sci U S A. 2008 Apr 1;105(13):5195-200 - PubMed
- Sci Rep. 2017 Nov 15;7(1):15653 - PubMed
- Nat Rev Immunol. 2008 Jan;8(1):48-58 - PubMed
- J Biol Chem. 2002 May 24;277(21):18769-76 - PubMed
- Curr Opin Cell Biol. 2012 Feb;24(1):107-15 - PubMed
- Methods Mol Biol. 2014;1100:355-64 - PubMed
- Proc Natl Acad Sci U S A. 2004 Oct 5;101 Suppl 2:14593-8 - PubMed
- J Leukoc Biol. 2010 Mar;87(3):397-403 - PubMed
- FEBS Lett. 1995 Aug 7;369(2-3):197-201 - PubMed
- J Biol Chem. 2004 Oct 22;279(43):44897-906 - PubMed
- J Exp Med. 1982 Jan 1;155(1):96-110 - PubMed
- Pediatr Res. 2017 Jul;82(1):63-71 - PubMed
- Immunology. 2010 Sep;131(1):141-51 - PubMed
- Biochim Biophys Acta. 2016 Oct;1861(10):1442-9 - PubMed
- Stroke. 1999 Jan;30(1):134-9 - PubMed
- J Immunol. 2009 Jun 1;182(11):6943-50 - PubMed
- J Cell Biol. 1994 Dec;127(6 Pt 2):2081-91 - PubMed
- J Biol Chem. 2000 Dec 8;275(49):38762-7 - PubMed
- J Clin Invest. 2004 Jun;113(11):1596-606 - PubMed
- Structure. 1995 Dec 15;3(12):1333-40 - PubMed
- J Immunol. 2002 Feb 1;168(3):1219-25 - PubMed
- J Biol Chem. 1994 Jun 3;269(22):15505-11 - PubMed
- Adv Drug Deliv Rev. 2012 Dec;64(15):1759-81 - PubMed
- J Immunol. 2004 Jun 1;172(11):7060-8 - PubMed
- Front Immunol. 2017 Dec 20;8:1866 - PubMed
- Biochemistry. 1994 Aug 23;33(33):10149-60 - PubMed
- J Immunol Res. 2016;2016:7675437 - PubMed
- Blood. 2018 Aug 30;132(9):962-972 - PubMed
- Expert Rev Clin Immunol. 2014 Sep;10(9):1151-64 - PubMed
- Semin Cell Dev Biol. 2017 Nov 24;:null - PubMed
- Nat Med. 2001 Jun;7(6):687-92 - PubMed
- Biophys J. 2008 Jan 15;94(2):656-60 - PubMed
- Mol Cell Proteomics. 2009 May;8(5):1044-60 - PubMed
- Int J Infect Dis. 2016 Jul;48:14-9 - PubMed
- J Cell Biol. 1990 Dec;111(6 Pt 2):3129-39 - PubMed
- Nat Rev Immunol. 2011 Jun;11(6):416-26 - PubMed
- Biophys J. 2003 Jun;84(6):4062-77 - PubMed
- Cell. 2003 Jan 10;112(1):99-111 - PubMed
- Immunol Rev. 2016 Jan;269(1):175-93 - PubMed
- Cell. 1995 Feb 24;80(4):631-8 - PubMed
- Biochem J. 1985 Oct 1;231(1):233-6 - PubMed
- Methods Mol Biol. 2012;757:55-71 - PubMed
- Nat Commun. 2018 Feb 6;9(1):525 - PubMed
- J Immunol. 2010 Oct 1;185(7):4154-68 - PubMed
- Annu Rev Immunol. 2011;29:215-33 - PubMed
- J Mol Biol. 2000 Feb 4;295(5):1251-64 - PubMed
- J Immunother. 2018 Jan;41(1):9-18 - PubMed
- Biochim Biophys Acta. 2007 Sep;1774(9):1148-55 - PubMed
- J Cell Biol. 1995 Sep;130(6):1473-82 - PubMed
- J Cell Biol. 2008 Aug 25;182(4):791-800 - PubMed
- Cell. 1993 Mar 26;72(6):857-67 - PubMed
- Biophys J. 2000 Jun;78(6):2814-20 - PubMed
- J Exp Med. 1982 Oct 1;156(4):1000-9 - PubMed
- J Biol Chem. 2012 Jan 27;287(5):3337-48 - PubMed
- J Cell Biol. 1992 Jan;116(1):219-26 - PubMed
- Mol Immunol. 2011 Oct;49(1-2):38-47 - PubMed
- J Biol Chem. 2013 Nov 8;288(45):32314-25 - PubMed
- Biosci Rep. 2012 Jun;32(3):241-69 - PubMed
- Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1614-9 - PubMed
- J Exp Med. 1990 May 1;171(5):1753-71 - PubMed
- EMBO J. 2010 Feb 3;29(3):666-79 - PubMed
- J Cell Physiol. 2013 Feb;228(2):306-12 - PubMed
- Structure. 1998 Jul 15;6(7):923-35 - PubMed
- Eur J Pharmacol. 2016 May 5;778:2-10 - PubMed
- Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):2940-5 - PubMed
- Immunol Res. 2002;25(3):219-27 - PubMed
- ACS Chem Biol. 2006 Nov 21;1(10):649-58 - PubMed
- Eur J Immunol. 1979 Apr;9(4):301-6 - PubMed
- Proc Natl Acad Sci U S A. 1997 Jan 7;94(1):65-72 - PubMed
- Biochem Biophys Res Commun. 1988 Oct 14;156(1):477-84 - PubMed
- Curr Opin Cell Biol. 2003 Oct;15(5):547-56 - PubMed
- J Am Chem Soc. 2006 Mar 22;128(11):3554-63 - PubMed
- J Immunol. 2008 Mar 15;180(6):3946-56 - PubMed
- Eur J Immunol. 1986 Sep;16(9):1117-23 - PubMed
- J Immunol. 2017 Jun 15;198(12):4855-4867 - PubMed
- J Cell Biol. 2013 Nov 25;203(4):629-42 - PubMed
- Cell Signal. 2013 Mar;25(3):609-14 - PubMed
- Mol Biol Cell. 2002 Oct;13(10):3369-87 - PubMed
- Langmuir. 2008 Oct 21;24(20):11577-86 - PubMed
- Science. 2011 Apr 29;332(6029):608-11 - PubMed
- Exp Cell Res. 2016 Mar 15;342(2):210-5 - PubMed
- J Clin Invest. 1993 Sep;92(3):1467-76 - PubMed
- Biochem Biophys Res Commun. 2015 Mar 6;458(2):251-5 - PubMed
- J Immunol. 1994 May 1;152(9):4582-9 - PubMed
- Cell. 2000 Mar 31;101(1):47-56 - PubMed
- Crit Rev Immunol. 1995;15(2):107-31 - PubMed
- J Biol Chem. 1990 Sep 25;265(27):16027-30 - PubMed
- Biochim Biophys Acta. 2016 May;1864(5):471-8 - PubMed
- Expert Opin Ther Targets. 2017 Jun;21(6):611-626 - PubMed
- Eur J Immunol. 2008 Aug;38(8):2263-73 - PubMed
- Annu Rev Immunol. 2000;18:393-422 - PubMed
- Scand J Immunol. 1991 Oct;34(4):381-9 - PubMed
- J Biol Chem. 2000 Jul 21;275(29):21877-82 - PubMed
- Proc Natl Acad Sci U S A. 2012 Dec 26;109(52):21420-5 - PubMed
- Xenobiotica. 2006 Apr;36(4):341-9 - PubMed
- Stroke. 2003 Nov;34(11):2543-8 - PubMed
- J Dent Res. 2015 Dec;94(12):1638-45 - PubMed
- Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):1044-8 - PubMed
- J Immunol. 2003 Dec 1;171(11):6135-44 - PubMed
- Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15062-7 - PubMed
- Blood. 2007 Jan 15;109(2):802-10 - PubMed
- Proc Natl Acad Sci U S A. 2000 May 9;97(10):5231-6 - PubMed
- Nature. 1990 Aug 2;346(6283):425-34 - PubMed
- Am J Health Syst Pharm. 2001 Nov 1;58 Suppl 2:S14-7 - PubMed
- Cold Spring Harb Symp Quant Biol. 1989;54 Pt 1:1-13 - PubMed
- Blood. 2011 May 5;117(18):4885-94 - PubMed
- Nat Struct Biol. 2000 Aug;7(8):674-8 - PubMed
- PLoS One. 2016 Feb 05;11(2):e0148486 - PubMed
- Clin Immunol. 2013 May;147(2):105-19 - PubMed
- Cell. 1994 Jan 28;76(2):301-14 - PubMed
- Proc Natl Acad Sci U S A. 2006 Apr 11;103(15):5758-63 - PubMed
- J Mol Recognit. 2003 Nov-Dec;16(6):412-21 - PubMed
- Eur J Immunol. 2001 Apr;31(4):1173-80 - PubMed
- Rheumatol Int. 2015 May;35(5):787-98 - PubMed
- Pharmaceuticals (Basel). 2016 Jul 04;9(3):null - PubMed
- Stroke. 1994 Apr;25(4):869-75; discussion 875-6 - PubMed
- J Mol Biol. 1999 Sep 10;292(1):1-9 - PubMed
- J Mol Biol. 2006 Oct 6;362(5):1132-47 - PubMed
- Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2906-11 - PubMed
- Mol Cell Ther. 2013 Nov 06;1:2 - PubMed
- J Biol Chem. 2012 Feb 10;287(7):4581-9 - PubMed
- J Immunol. 2001 Aug 1;167(3):1490-9 - PubMed
- J Immunol. 1986 Jan;136(1):240-5 - PubMed
- Proc Natl Acad Sci U S A. 2017 Mar 28;114(13):3403-3408 - PubMed
- Biochim Biophys Acta Biomembr. 2017 Mar;1859(3):425-437 - PubMed
- Clin Exp Immunol. 2017 Nov;190(2):258-267 - PubMed
- Biochim Biophys Acta. 2015 Aug;1854(8):930-8 - PubMed
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