[PDF][PDF] Siderocalin (Lcn 2) also binds carboxymycobactins, potentially defending against mycobacterial infections through iron sequestration

MA Holmes, W Paulsene, X Jide, C Ratledge… - Structure, 2005 - cell.com
MA Holmes, W Paulsene, X Jide, C Ratledge, RK Strong
Structure, 2005cell.com
Siderocalin, a member of the lipocalin family of binding proteins, is found in neutrophil
granules, uterine secretions, and at markedly elevated levels in serum and synovium during
bacterial infection; it is also secreted from epithelial cells in response to inflammation or
tumorigenesis. Identification of high-affinity ligands, bacterial catecholate-type siderophores
(such as enterochelin), suggested a possible function for siderocalin: an antibacterial agent,
complementing the general antimicrobial innate immune system iron-depletion strategy …
Summary
Siderocalin, a member of the lipocalin family of binding proteins, is found in neutrophil granules, uterine secretions, and at markedly elevated levels in serum and synovium during bacterial infection; it is also secreted from epithelial cells in response to inflammation or tumorigenesis. Identification of high-affinity ligands, bacterial catecholate-type siderophores (such as enterochelin), suggested a possible function for siderocalin: an antibacterial agent, complementing the general antimicrobial innate immune system iron-depletion strategy, sequestering iron as ferric siderophore complexes. Supporting this hypothesis, siderocalin is a potent bacteriostatic agent in vitro under iron-limiting conditions and, when knocked out, renders mice remarkably susceptible to bacterial infection. Here we show that siderocalin also binds soluble siderophores of mycobacteria, including M. tubercu losis: carboxymycobactins. Siderocalin employs a degenerate recognition mechanism to cross react with these dissimilar types of siderophores, broadening the potential utility of this innate immune defense.
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