Structure and mechanism of receptor sharing by the IL-10R2 common chain.
IL-10R2 is a shared cell surface receptor required for the activation of five class 2 cytokines (IL-10, IL-22, IL-26, IL-28, and IL-29) that play critical roles in host defense. To define the molecular mechanisms that regulate its promiscuous binding, we have determined the crystal structure of the IL-10R2 ectodomain at 2.14 A resolution. IL-10R2 residues required for binding were identified by alanine scanning and used to derive computational models of IL-10/IL-10R1/IL-10R2 and IL-22/IL-22R1/IL-10R2 ternary complexes. The models reveal a conserved binding epitope that is surrounded by two clefts that accommodate the structural and chemical diversity of the cytokines. These results provide a structural framework for interpreting IL-10R2 single nucleotide polymorphisms associated with human disease.
Yoon
Sung-Il
SI
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Jones
Brandi C
BC
Logsdon
Naomi J
NJ
Harris
Bethany D
BD
Deshpande
Ashlesha
A
Radaeva
Svetlana
S
Halloran
Brian A
BA
Gao
Bin
B
Walter
Mark R
MR
D000409:Alanine / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D007378:Interleukins; D011485:Protein Binding / Q000235:genetics; D018123:Receptors, Interleukin; D000097043:Interleukin-22
D000409:Alanine; D016207:Cytokines; D016753:Interleukin-10; D007378:Interleukins; D018123:Receptors, Interleukin; D000097043:Interleukin-22; C415369:interleukin-22 receptor
Acta Crystallogr D Biol Crystallogr. 1994 Sep 1;50(Pt 5):760-3
15299374
Immunity. 2001 Jul;15(1):35-46
11485736
Nucleic Acids Res. 2006 Jul 04;34(11):3317-25
16820531
Genes Immun. 2005 Feb;6(1):8-18
15526001
Acta Crystallogr D Biol Crystallogr. 1993 Jan 1;49(Pt 1):129-47
15299554
Methods Enzymol. 1997;276:307-26
27754618
Nature. 1998 Oct 1;395(6701):511-6
9774108
EMBO J. 1997 Oct 1;16(19):5894-903
9312047
Protein Expr Purif. 2007 May;53(1):132-7
17224278
Annu Rev Immunol. 2001;19:683-765
11244051
Acta Crystallogr D Biol Crystallogr. 1996 Jan 1;52(Pt 1):30-42
15299723
Nat Immunol. 2003 Jan;4(1):69-77
12483210
FEBS Lett. 2008 Sep 3;582(20):2985-92
18675809
Hepatology. 2004 May;39(5):1332-42
15122762
Science. 1999 Feb 12;283(5404):987-90
9974392
J Leukoc Biol. 2004 Aug;76(2):314-21
15123776
Immunity. 2007 Oct;27(4):647-59
17919941
J Mol Graph. 1996 Feb;14(1):33-8, 27-8
8744570
Nature. 2009 Sep 17;461(7262):399-401
19684573
Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21
9757107
Nat Struct Mol Biol. 2005 Sep;12(9):814-21
16116438
Blood. 2005 Dec 1;106(12):3995-4001
16109775
Structure. 2005 Apr;13(4):551-64
15837194
Biochem Biophys Res Commun. 2008 Aug 29;373(3):403-7
18588853
Proc Natl Acad Sci U S A. 1989 Sep;86(17):6592-6
2771946
Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9148-53
16757563
J Mol Biol. 2004 Sep 10;342(2):503-14
15327950
J Exp Med. 2000 Jan 17;191(2):213-24
10637267
Gut. 2009 Sep;58(9):1207-17
18483078
Trends Microbiol. 2007 Apr;15(4):143-6
17336072
J Biol Chem. 2001 Jan 26;276(4):2725-32
11035029
Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9404-9
12093920
Bioinformatics. 2006 Oct 01;22(19):2340-7
16899489
Acta Crystallogr D Biol Crystallogr. 1997 Jul 1;53(Pt 4):448-55
15299911
N Engl J Med. 2009 Nov 19;361(21):2033-45
19890111
J Biol Chem. 2000 Sep 29;275(39):30100-5
10887198
Trends Microbiol. 2001 Feb;9(2):86-92
11173248
Adv Protein Chem. 2004;68:171-223
15500862
Structure. 2008 Sep 10;16(9):1333-44
18599299
J Exp Med. 2006 Oct 2;203(10):2271-9
16982811
J Immunol. 1995 Aug 1;155(3):1079-90
7543512
J Immunol. 2001 Oct 1;167(7):3545-9
11564763
Proteins. 1992 Oct;14(2):309-23
1409577
Annu Rev Immunol. 2009;27:29-60
18817510
J Biol Chem. 2000 Oct 6;275(40):31335-9
10875937
J Immunol. 2004 Feb 15;172(4):2006-10
14764663
J Immunol. 1999 Feb 1;162(3):1480-7
9973404
BMC Struct Biol. 2005 Jun 28;5:10
15985167
Acta Crystallogr D Biol Crystallogr. 1999 Apr;55(Pt 4):849-61
10089316
BMC Immunol. 2009 May 04;10:24
19409109
Nat Immunol. 2003 Jan;4(1):63-8
12469119
J Biol Chem. 1996 Jun 14;271(24):14045-54
8662939
J Virol. 2009 Oct;83(19):9618-29
19640997
Science. 1992 Jan 17;255(5042):306-12
1549776
Science. 2003 Jun 27;300(5628):2101-4
12829785
Science. 1995 Jan 20;267(5196):383-6
7529940
J Mol Biol. 2008 Oct 24;382(5):1168-83
18675824
J Biol Chem. 2006 Nov 17;281(46):35088-96
16982608
J Am Chem Soc. 2003 Feb 19;125(7):1731-7
12580598
J Interferon Cytokine Res. 2002 Nov;22(11):1099-112
12513909