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Báo cáo khoa học: Molecular basis of cytokine signalling – theme and variations

Cytokine receptors are crucial for the maintenance, regulation and growth of cells in multicellular organisms. As a common theme in cytokine signal-ling, single-span receptor chains are assembled in the cell membrane by a ligand enabling cross-activation of the aligned cytoplasmic receptor domains. | THE THEODOR BUCHER LECTURE Molecular basis of cytokine signalling - theme and variations Delivered on 8 July 2009 at the 34th FEBS Congress in Prague Walter Sebald1 Joachim Nickel1 Jin-Li Zhang2 and Thomas D. Mueller3 1 Department of PhysiologicalChemistry II Theodor-Boveri Institute for Life Sciences Biocenter University of Wuerzburg Germany 2 Institute for DevelopmentalBiology University of Cologne Germany 3 Department of Molecular Plant Physiology and Biophysics Julius-von-Sachs Institute University of Wuerzburg Germany Keywords bone morphogenetic proteins BMP drug development interleukins molecular recognition receptor oligomers Correspondence W. Sebald Department of Physiological Chemistry II Theodor-Boveri Institute for Life Sciences Biocenter University of Wuerzburg Am Hubland 97074 Wuerzburg Germany Fax 49 931 8884113 Tel 49 931 3188322 E-mail sebald@biozentrum.uni-wuerzburg.de Received 27 July 2009 revised 28 September 2009 accepted 4 November 2009 doi 10.1111 j.1742-4658.2009.07480.x Cytokine receptors are crucial for the maintenance regulation and growth of cells in multicellular organisms. As a common theme in cytokine signalling single-span receptor chains are assembled in the cell membrane by a ligand enabling cross-activation of the aligned cytoplasmic receptor domains. Nature has created many variations of how this general principle is realized in a cell. Here we focus on cytokines of the four-helix bundle interleukins and cystine knot transforming growth factor- p bone morphogenetic proteins families. Upon activation receptor chains can form duos trios quartets and even larger assemblies. The structure of the extracellular ligand-binding domain of a number of these receptor complexes has now been elucidated providing the molecular basis for understanding the functional relevance of mechanistic diversity in a cellular context. Biochemical and structural data have revealed ligand recognition mechanisms. Contact sites are usually large and rather .