2. CD23: A lectin as an Fc receptor for IgE
The CD23 molecule is a trimeric glycoprotein member of the
calcium-dependent (C-type) lectin family with a 45 kDa subunit. However,
despite the fact that CD23 is a C-type lectin and IgE is heavily
glycosylated, the interaction between IgE and CD23 is independent of
carbohydrates (28). Structurally, CD23 presents a short cytoplasmic
N-terminus followed by a single transmembrane region and a long
C-terminal extracellular domain (29). The extracellular part consists of
three regions: 1) an alpha-helical coiled-coil stalk region which
mediates the formation of trimers, 2) lectin head which binds IgE and 3)
a modified RGD sequence that binds to α5β5 integrin (30). There are two
major CD23 isoforms, CD23a and CD23b(31) which only differ in their
intracellular region only 21 or 22 amino acids long for CD23a and CD23b,
respectively. CD23 is expressed initially as a membrane-bound molecule
but it may be cleaved from the cell surface by metalloproteinases such
as ADAM-10 resulting in soluble CD23 fragments (sCD23) of different
molecular weights (37,33, 25 and 17 kDa) (32,33).
Structural studies have shown that IgE interacts in different manners
with its two receptors, FcεRI and CD23 (34). IgE binds to FcεRI with
high affinity (KD between 0.01 nM to 0.1nM). This occurs
through the Cε3 domain in an open conformation allowing the binding of
the FcεRI to a binding pocket formed by two sub-sides 1 (Cε3A) and 2
(Cε3B) (35,36). In contrast, in case of CD23 the crystal structure of
the complex shows the interaction of two CD23 heads binding to Cε3 and
Cε4 domains of a single IgE molecule with different affinities. One
binding site has an affinity of around 1 µM whereas the other one
differs by one order of magnitude weaker (KD around 14.4
µM) (37–39). This interaction is characterized by bringing two Cε3
domains together in a “closed” conformation incompatible with the
binding to FcεRIα. The second major ligand of CD23 is CD21. It was shown
that the CD21 binding site on CD23 does not overlap with IgE binding
sites (40,41). For CD23 and CD21, a carbohydrate-dependent interaction
was reported (42).