title: The v-myc-induced Q83 lipocalin is a siderocalin.
abstract: Siderocalins are atypical lipocalins able to capture siderophores with high affinity. They contribute to the innate immune response by interfering with bacterial siderophore-mediated iron uptake but are also involved in numerous physiological processes such as inflammation, iron delivery, tissue differentiation, and cancer progression. The Q83 lipocalin was originally identified based on its overexpression in quail embryo fibroblasts transformed by the v-myc oncogene. We show here that Q83 is a siderocalin, binding the siderophore enterobactin with an affinity and mode of binding nearly identical to that of neutrophil gelatinase-associated lipocalin (NGAL), the prototypical siderocalin. This strengthens the role of siderocalins in cancer progression and inflammation. In addition, we also present the solution structure of Q83 in complex with intact enterobactin and a detailed analysis of the Q83 binding mode, including mutagenesis of the critical residues involved in enterobactin binding. These data provide a first insight into the molecular details of siderophore binding and delineate the common molecular properties defining the siderocalin protein family.
authors.affiliation: Department of Structural and Computational Biology, Max F Perutz Laboratories, University of Vienna, 1030 Vienna, Austria. nicolas.coudevylle@univie.ac.at
authors.forename: Nicolas
authors.initials: N
authors.lastname: Coudevylle
authors.forename: Leonhard
authors.initials: L
authors.lastname: Geist
authors.forename: Matthias
authors.initials: M
authors.lastname: Hötzinger
authors.forename: Markus
authors.initials: M
authors.lastname: Hartl
authors.forename: Georg
authors.initials: G
authors.lastname: Kontaxis
authors.forename: Klaus
authors.initials: K
authors.lastname: Bister
authors.forename: Robert
authors.initials: R
authors.lastname: Konrat
mesh_terms: D000209:Acute-Phase Proteins / Q000737:chemistry; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry*; D018450:Disease Progression; D016259:Genes, myc; D006801:Humans; D007249:Inflammation; D000071068:Lipocalin-2; D054834:Lipocalins / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000737:chemistry; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry*; D011784:Quail; D017386:Sequence Homology, Amino Acid
chemical_list: D000209:Acute-Phase Proteins; D002352:Carrier Proteins; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc
references.citation: J Bacteriol. 2004 Sep;186(17):5826-33
references.pmid: 15317788
references.citation: Eur J Cell Biol. 2002 May;81(5):264-72
references.pmid: 12067062
references.citation: J Immunol. 2009 Apr 15;182(8):4947-56
references.pmid: 19342674
references.citation: Biometals. 2009 Aug;22(4):557-64
references.pmid: 19184458
references.citation: J Magn Reson B. 1996 May;111(2):199-203
references.pmid: 8661282
references.citation: J Bacteriol. 2005 Oct;187(19):6701-7
references.pmid: 16166532
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):3584-8
references.pmid: 12655062
references.citation: J Biomol NMR. 2002 Nov;24(3):171-89
references.pmid: 12522306
references.citation: J Mol Biol. 2002 May 24;319(1):209-27
references.pmid: 12051947
references.citation: J Am Chem Soc. 2003 Feb 19;125(7):1731-7
references.pmid: 12580598
references.citation: J Am Chem Soc. 2008 Aug 27;130(34):11524-34
references.pmid: 18680288
references.citation: J Biomol NMR. 1998 Oct;12(3):361-72
references.pmid: 9835045
references.citation: Immunobiology. 2008;213(9-10):879-88
references.pmid: 18926302
references.citation: J Biomol NMR. 1999 Mar;13(3):289-302
references.pmid: 10212987
references.citation: Structure. 2005 Jan;13(1):29-41
references.pmid: 15642259
references.citation: J Mol Biol. 2003 Oct 10;333(1):33-46
references.pmid: 14516741
references.citation: Biochim Biophys Acta. 2000 Oct 18;1482(1-2):9-24
references.pmid: 11058743
references.citation: Biochem J. 2007 Apr 15;403(2):297-303
references.pmid: 17253959
references.citation: J Cell Biol. 1988 Dec;107(6 Pt 1):2455-63
references.pmid: 3143737
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3913-8
references.pmid: 19237579
references.citation: Acta Crystallogr D Biol Crystallogr. 2004 Aug;60(Pt 8):1355-63
references.pmid: 15272157
references.citation: Eur J Cell Biol. 2000 Mar;79(3):155-64
references.pmid: 10777107
references.citation: J Mol Med (Berl). 2009 Aug;87(8):803-13
references.pmid: 19466389
references.citation: Bioinformatics. 2008 Feb 1;24(3):426-7
references.pmid: 18174182
references.citation: Bioinformatics. 2008 Mar 15;24(6):872-3
references.pmid: 18227113
references.citation: Oncogene. 2008 Oct 16;27(47):6110-9
references.pmid: 18663364
references.citation: Mol Cell. 2002 Nov;10(5):1033-43
references.pmid: 12453412
references.citation: J Am Chem Soc. 2008 Dec 24;130(51):17584-92
references.pmid: 19053425
references.citation: Biochem J. 1996 Aug 15;318 ( Pt 1):1-14
references.pmid: 8761444
references.citation: J Bacteriol. 2004 Jun;186(11):3578-89
references.pmid: 15150246
references.citation: J Biomol NMR. 1995 Nov;6(3):277-93
references.pmid: 8520220
references.citation: Antimicrob Agents Chemother. 2004 Sep;48(9):3367-72
references.pmid: 15328098
references.citation: Cell. 2005 Dec 29;123(7):1293-305
references.pmid: 16377569
references.citation: FEBS Lett. 1994 Oct 31;354(1):7-11
references.pmid: 7957904
references.citation: Biochim Biophys Acta. 2000 Oct 18;1482(1-2):298-307
references.pmid: 11058770
references.citation: Anal Biochem. 1987 Jan;160(1):47-56
references.pmid: 2952030
references.citation: J Am Chem Soc. 2006 Aug 30;128(34):10998-9
references.pmid: 16925397
references.citation: Biochim Biophys Acta. 1970 Aug 14;215(2):393-402
references.pmid: 4926450
references.citation: J Biol Chem. 2004 Aug 20;279(34):35890-902
references.pmid: 15169787
references.citation: Nat Protoc. 2008;3(4):679-90
references.pmid: 18388951
references.citation: Proc Natl Acad Sci U S A. 2006 Feb 7;103(6):1834-9
references.pmid: 16446425
references.citation: J Biomol NMR. 2001 Oct;21(2):107-16
references.pmid: 11727974
references.citation: Annu Rev Biochem. 1981;50:715-31
references.pmid: 6455965
references.citation: Eur J Cell Biol. 1989 Oct;50(1):154-61
references.pmid: 2693089
references.citation: Mol Cell. 2002 Nov;10(5):1045-56
references.pmid: 12453413
references.citation: EMBO J. 2009 Apr 8;28(7):866-76
references.pmid: 19229297
references.citation: Am J Physiol Renal Physiol. 2003 Jul;285(1):F9-18
references.pmid: 12788784
references.citation: Nature. 2004 Dec 16;432(7019):917-21
references.pmid: 15531878
references.citation: J Exp Clin Cancer Res. 2008 Dec 12;27:83
references.pmid: 19077278
references.citation: PLoS Pathog. 2009 Oct;5(10):e1000622
references.pmid: 19834550
references.citation: J Magn Reson. 2003 Jan;160(1):65-73
references.pmid: 12565051
references.citation: Proteins. 2007 Dec 1;69(4):726-33
references.pmid: 17803234