Theoretical investigation of IL-6 multiprotein receptor assembly.
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-6R alpha: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-6R alpha) 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.
Menziani
M C
MC
Dipartimento di Chimica, Università di Modena, Italy.
Fanelli
F
F
De Benedetti
P G
PG
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry; D001665:Binding Sites; D002417:Cattle; D018360:Crystallography, X-Ray; D050822:Cytokine Receptor gp130; D019281:Dimerization; D004285:Dogs; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry*; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D017434:Protein Structure, Tertiary; D019947:Receptors, Interleukin-6 / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
D015703:Antigens, CD; C494199:IL6ST protein, human; C494200:Il6st protein, mouse; D015850:Interleukin-6; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D046912:Multiprotein Complexes; D019947:Receptors, Interleukin-6; D050822:Cytokine Receptor gp130