Solution assembly of the pseudo-high affinity and intermediate affinity interleukin-2 receptor complexes.
The high affinity interleukin-2 receptor is composed of three cell surface subunits, IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma. Functional forms of the IL-2 receptor exist, however, that enlist only two of the three subunits. On activated T-cells, the alpha- and beta-subunits combine as a preformed heterodimer (the pseudo-high affinity receptor) that serves to capture IL-2. On a subpopulation of natural killer cells, the beta- and gamma-subunits interact in a ligand-dependent manner to form the intermediate affinity receptor site. Previously, we have demonstrated the feasibility of employing coiled-coil molecular recognition for the solution assembly of a heteromeric IL-2 receptor complex. In that study, although the receptor was functional, the coiled-coil complex was a trimer rather than the desired heterodimer. We have now redesigned the hydrophobic heptad sequences of the coiled-coils to generate soluble forms of both the pseudo-high affinity and the intermediate affinity heterodimeric IL-2 receptors. The properties of these complexes were examined and their relevance to the physiological IL-2 receptor mechanism is discussed.
Wu
Z
Z
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.
Goldstein
B
B
Laue
T M
TM
Liparoto
S F
SF
Nemeth
M J
MJ
Ciardelli
T L
TL
D000595:Amino Acid Sequence; D001667:Binding, Competitive; D001704:Biopolymers / Q000737:chemistry; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011869:Radioligand Assay; D015375:Receptors, Interleukin-2 / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D012996:Solutions; D014461:Ultracentrifugation
D001704:Biopolymers; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D012996:Solutions