Biology Reference
In-Depth Information
4.1 Siderocalin
The lipocalin family of extracellular proteins has functions that vary significantly
among the proteins within this family. From promoting organogenesis and deliv-
ering hydrophobic ligands in cell signaling to facilitating biosynthesis and par-
ticipating in immunodefense, the lipocalins serve both eukaryotic and prokaryotic
organisms [
1
-
3
]. Despite the diversity of lipocalin functions, these proteins share
up to three structurally conserved regions. A characteristic feature of all lipocalins
is a barrel formed by eight-stranded anti-parallel beta sheets (Fig.
4.1
). The inte-
rior binding sites of lipocalins are generally lined with positively charged amino
acid residues which create binding interactions with a substrate.
The lipocalin now called siderocalin (Scn) has been known for several decades
and designated variously as 24p3, uterocalin, lipocalin 2 (Lcn2), human neutrophil
lipocalin (HNL) and neutrophil gelatinase associated lipocalin (NGAL). However,
a specific function for it was not fully elucidated until Goetz et al. [
4
] provided
solid-state and solution structural evidence that bacteria-derived ferric enterobac-
tin was complementarily bound to the Scn binding pocket (Fig.
4.1
). The most
important result from these studies and others which soon followed was that Scn
participates in the acute immune response to bacterial infections by sequestering
certain ferric siderophores and thus restricting iron piracy and subsequent prolif-
eration by bacteria [
4
,
5
]. For example, the growth of mycobacterial strains in vitro
in murine macrophage cell lines was inhibited by addition of recombinant Scn [
6
].
Scn is also successful in vivo, decreasing the susceptibility of murine models to
both
Escherichia coli
and
Mycobacterium tuberculosis
[
5
,
6
]. Other experiments
show that Scn-knockout mice have increased susceptibility to bacterial infections
Fig. 4.1
Ribbon-drawing diagram of Scn (
left
) and schematic drawing of Scn with bound ferric-
enterobactin (
right
)
Search WWH ::
Custom Search