INTERLEUKIN-5 (IL-5) specifically induces the differentiation of eosin
ophils, which are important in host defence and the patho genesis of a
llergies and asthma(1,2). Structurally, IL-5 is a unique member of the
short-chain helical-bundle subfamily of cytokines whose canonical mot
if contains four helices (A-D) arranged in an up-up-down-down topology
(3,4). In contrast to other subfamily members, which fold unimolecular
ly into a single helical bundle(5-8), IL-5 forms a pair of helical bun
dles by the interdigitation of two identical monomers that contribute
a D helix to the other's A-C helices(3). We predicted that the lack of
bioactivity by an IL-5 monomer(9) was due to a short loop between hel
ices C and D which physically prevents unimolecular folding of helix D
into a functionally obligate structural motif. Here we report that, b
y lengthening this loop, we have engineered an insertional mutant of I
L-5 that was expressed as a monomer with biological activity similar t
o that of native IL-5. These studies demonstrate that all of the struc
tural features necessary for IL-5 to function are contained within a s
ingle helical bundle.