title: Iron traffics in circulation bound to a siderocalin (Ngal)-catechol complex.
abstract: The lipocalins are secreted proteins that bind small organic molecules. Scn-Ngal (also known as neutrophil gelatinase associated lipocalin, siderocalin, lipocalin 2) sequesters bacterial iron chelators, called siderophores, and consequently blocks bacterial growth. However, Scn-Ngal is also prominently expressed in aseptic diseases, implying that it binds additional ligands and serves additional functions. Using chemical screens, crystallography and fluorescence methods, we report that Scn-Ngal binds iron together with a small metabolic product called catechol. The formation of the complex blocked the reactivity of iron and permitted its transport once introduced into circulation in vivo. Scn-Ngal then recycled its iron in endosomes by a pH-sensitive mechanism. As catechols derive from bacterial and mammalian metabolism of dietary compounds, the Scn-Ngal-catechol-Fe(III) complex represents an unforeseen microbial-host interaction, which mimics Scn-Ngal-siderophore interactions but instead traffics iron in aseptic tissues. These results identify an endogenous siderophore, which may link the disparate roles of Scn-Ngal in different diseases.
authors.affiliation: College of Physicians and Surgeons of Columbia University, New York, New York, USA.
authors.forename: Guanhu
authors.initials: G
authors.lastname: Bao
authors.forename: Matthew
authors.initials: M
authors.lastname: Clifton
authors.forename: Trisha M
authors.initials: TM
authors.lastname: Hoette
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Mori
authors.forename: Shi-Xian
authors.initials: SX
authors.lastname: Deng
authors.forename: Andong
authors.initials: A
authors.lastname: Qiu
authors.forename: Melanie
authors.initials: M
authors.lastname: Viltard
authors.forename: David
authors.initials: D
authors.lastname: Williams
authors.forename: Neal
authors.initials: N
authors.lastname: Paragas
authors.forename: Thomas
authors.initials: T
authors.lastname: Leete
authors.forename: Ritwij
authors.initials: R
authors.lastname: Kulkarni
authors.forename: Xiangpo
authors.initials: X
authors.lastname: Li
authors.forename: Belinda
authors.initials: B
authors.lastname: Lee
authors.forename: Avtandil
authors.initials: A
authors.lastname: Kalandadze
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ratner
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Pizarro
authors.forename: Kai M
authors.initials: KM
authors.lastname: Schmidt-Ott
authors.forename: Donald W
authors.initials: DW
authors.lastname: Landry
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Raymond
authors.forename: Roland K
authors.initials: RK
authors.lastname: Strong
authors.forename: Jonathan
authors.initials: J
authors.lastname: Barasch
mesh_terms: D000209:Acute-Phase Proteins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002396:Catechols / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D019295:Computational Biology; D018360:Crystallography, X-Ray; D011992:Endosomes / Q000378:metabolism; D005456:Fluorescent Dyes; D006801:Humans; D007501:Iron / Q000097:blood* / Q000737:chemistry; D007502:Iron Chelating Agents / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008024:Ligands; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D015513:Oncogene Proteins / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry; D017262:Siderophores / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D002396:Catechols; D005456:Fluorescent Dyes; D007502:Iron Chelating Agents; D008024:Ligands; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011994:Recombinant Proteins; D017262:Siderophores; C071332:Lcn2 protein, mouse; D007501:Iron