STRUCTURE OF CYTOKINE HYDROPHOBIC CORES

Diagrams were constructed that describe, using a common frame of refer ence, the interactions that occur within the hydrophobic cores of the left-handed four-helix bundles of interleukin-2, -4, -5, granulocyte/m acrophage-, granulocyte-, macrophage-colony-stimulating factor, beta- and gamma-interferon, growth hormone, and leukemia inhibitory factor. Based on the assumption that the topologies of the ligand-receptor com plexes are similar, analogous patterns were obtained from these diagra ms and lead to the detailed comparison of the hydrophobic cores. These patterns were then used to obtain pairwise rigid-body superpositions among all of the four-helix bundles: values of the root-mean-square de viations (C alpha-atoms) over the four alpha-helices of the bundles ra nge from 1.14 Angstrom to 3.22 Angstrom. Two distinct groups are forme d after clustering based on structural superposition of the ten cytoki nes. (C) 1996 Academic Press Limited.