The structure of interleukin-2 complexed with its alpha receptor

Science. 2005 Jun 3;308(5727):1477-80. doi: 10.1126/science.1109745.

Abstract

Interleukin-2 (IL-2) is an immunoregulatory cytokine that binds sequentially to the alpha (IL-2Ralpha), beta (IL-2Rbeta), and common gamma chain (gammac) receptor subunits. Here we present the 2.8 angstrom crystal structure of a complex between human IL-2 and IL-2Ralpha, which interact in a docking mode distinct from that of other cytokine receptor complexes. IL-2Ralpha is composed of strand-swapped "sushi-like" domains, unlike the classical cytokine receptor fold. As a result of this domain swap, IL-2Ralpha uses a composite surface to dock into a groove on IL-2 that also serves as a binding site for antagonist drugs. With this complex, we now have representative structures for each class of hematopoietic cytokine receptor-docking modules.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Crystallography, X-Ray
  • Humans
  • Interleukin-2 / chemistry*
  • Interleukin-2 / metabolism
  • Interleukin-2 Receptor alpha Subunit
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Receptors, Interleukin / chemistry*
  • Receptors, Interleukin / metabolism

Substances

  • IL2RA protein, human
  • Interleukin-2
  • Interleukin-2 Receptor alpha Subunit
  • Receptors, Interleukin

Associated data

  • PDB/1Z92