A structural template for gp130-cytokine signaling assemblies.
The gp130-cytokine system has been fertile ground for protein structure-function studies aimed at elucidating the basis of ligand recognition and receptor activation. A number of longstanding questions involve the mechanism of the stepwise assembly of the active signaling complexes, as well as the structure of the gp130-cytokine complexes. It has been clear from functional studies that the paradigm of gp130-cyokine recognition will differ substantially from the classical homo-dimeric systems, typified by human growth hormone (hGH) and its receptor. Recently, a crystal structure of a viral interleukin-6 (vIL-6), complexed with the D1D2D3 domains of the gp130 extracellular domain, has resolved many of these questions, and reconciled much of the functional and mutagenesis data which have existed for a variety of gp130-cytokines. In this review, we discuss the structure of the vIL-6/gp130 complex in some detail and suggest that the geometry of this complex will be a common structural template utilized by other gp130-cytokines, as well as cytokines from distinct signaling systems.
Chow
Dar-chone
DC
Deparment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305-5124, USA.
Brevnova
Lena
L
He
Xiao-lin
XL
Martick
Monika M
MM
Bankovich
Alex
A
Garcia
K Christopher
KC
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry* / Q000502:physiology*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D050822:Cytokine Receptor gp130; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D015850:Interleukin-6 / Q000737:chemistry*; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000502:physiology*; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D018121:Receptors, Cytokine / Q000737:chemistry; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014764:Viral Proteins / Q000737:chemistry*
D015703:Antigens, CD; D000939:Epitopes; C494199:IL6ST protein, human; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D018121:Receptors, Cytokine; D014764:Viral Proteins; D050822:Cytokine Receptor gp130