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Theoretical investigation of IL‐6 multiprotein receptor assembly
Author(s) -
Menziani M.C.,
Fanelli F.,
De Benedetti P.G.
Publication year - 1997
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(199712)29:4<528::aid-prot12>3.0.co;2-o
Subject(s) - multiprotein complex , glycoprotein 130 , receptor , microbiology and biotechnology , cytokine , biology , computational biology , chemistry , genetics , interleukin 6 , gene
Interleukin‐6 (IL‐6) is a multifunctional cytokine that regulates cell growth, differentiation, and cellular functions in many cell lineages. Recently, evidences for the formation of an active hexameric complex with an IL‐6:IL‐6Rα:gp130 stoichiometry of 2:2:2 have been obtained by different experimental approaches. Analysis of the electrostatic potential complementarity between IL‐6 and its receptors has been used, in this study, to guide the assembly of homology‐based 3D models of the components. The results strongly support a mechanism whereby the active cytokine (IL‐6:IL‐6Rα) associates with the signal transducing gp130 protein, and the trimeric complex formed further dimerizes to form the hexameric species. Furthermore, computational simulations of the multiprotein complexes provide a rationalization of data from mutation experiments and highlight some key protein–protein interactions which have not yet been the subject of mutagenesis studies. Proteins 29:528–544, 1997. © 1997 Wiley‐Liss, Inc.