122
Cytokines: Interleukins
CYS58
CYS105
CYS58
CYS105
EE
C
D
BA
FC
D
B
A
F
B'
B'
Fig. 1
Schematic stereo drawing of IL-2; helices are represented
as cylinders and are lettered sequentially from the N-terminus.
(Reprinted with permission from Brandhuber et al. (1987)
Science
238
, 1707. Copyright 1987 by American Association for
the Advancement of Science.)
receptors for these interleukins also have
common features (discussed in Sect. 3.1).
These interleukins have sometimes been
referred to as
hematopoietins
and their re-
ceptors as hematopoietin receptors (HR).
Interestingly,
the
hematopoietin family
extends to other noninterleukin media-
tors such as erythropoietin (EPO) and
growth
hormone
(GH)
as
well
as
a
number of cytokines, including granulo-
cyte colony stimulating factor (G-CSF),
granulocyte-macrophage colony stimulat-
ing factor (GM-CSF), leukemia inhibitory
factor (LIF), oncostatin M (OSM), and
ciliary
neurotrophic
factor
(CNTF).
In
contrast,
IL-1ß
and
other
IL-1
family
members
are
nonhelical proteins
with
about 60% of residues in ß-strands, in
a compact con±guration known as a ß-
trefoil (Fig. 2). IL-1
α
and ß and IL-18
are also unlike the other interleukins in
having long N-terminal leader sequences
(prodomains) rather than the recogniz-
able signal polypeptides of secreted in-
terleukins. Their processing and the exit
of mature IL-1
α
, IL-1ß, or IL-18 from
cells is therefore quite different from the
other interleukins. A speci±c enzyme, a
cysteine protease originally called IL-1ß
converting enzyme but now designated
caspase 1, which cleaves pro-IL-1ß to re-
lease the mature (active) IL-1ß protein,
has
been
characterized.
The
IL-8
pro-
tein
has
a
structure
that
incorporates
both
α
-helical and ß-strand domains. The
three-dimensional structures of the latest
additions to the interleukin family are not
known in detail, but are predicted to be
mainly
α
-helical.
Another variable characteristic of in-
terleukins is whether they are active in
the monomeric or dimeric con±guration.
Most are active as monomers, but IL-5,
IL-8, IL-10, (and IL-19, IL-20, IL-22, IL-
24, IL-26) and IL-12 (and IL-23, IL-27) are
dimers. Glycosylation is also a variable fea-
ture of interleukins; IL-1
α
and ß are not
glycosylated, whereas most of the other
interleukins have either O-linked and/or
N-linked oligosaccharide side chains. The
molecular characteristics of interleukins
are summarized in Table 2.
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