PMID: 9192627Jun 24, 1997Paper

Monomeric isomers of human interleukin 5 show that 1:1 receptor recruitment is sufficient for function

Proceedings of the National Academy of Sciences of the United States of America
J LiI Chaiken

Abstract

The normally dimeric human interleukin 5 (IL-5) was re-engineered into two monomeric isomer forms to investigate mechanistic features of receptor recognition. One form, denoted GM1-IL-5, is a CD-loop expanded form, in which an 8-residue linker designed for flexibility was inserted between residues 85 and 86. The second, denoted DABC-IL-5, is a circularly permuted form of human IL-5 in which a chain discontinuity was introduced in the CD loop and the two consequent chain fragments were joined at the normal N and C termini by a di-glycyl linker. Both IL-5 isomers folded into stable monomers in solution as shown by sedimentation equilibrium and CD and formed an intrachain disulfide bond predicted from the structure of wild type IL-5. From titration microcalorimetry and optical biosensor analyses, both monomers were shown to interact with the IL-5 receptor alpha chain with 1:1 stoichiometry and affinities 30- to 40-fold weaker than for the dimeric wild type protein. And both monomers stimulated cell proliferation of human IL-5 receptor positive cells with a concentration dependence close to that of wild type. The data show that both monomeric and dimeric forms of IL-5 function through similar 1:1 receptor alpha chain recruitment pr...Continue Reading

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Citations

Mar 31, 1998·Current Opinion in Structural Biology·J H Lakey, E M Raggett
Mar 7, 2012·Developmental and Comparative Immunology·Yuji FukushimaShuichi Furusawa
Sep 8, 2000·Cytokine·S ZahnI Chaiken
May 2, 2000·The Journal of Biological Chemistry·K JosephsonA H Ayo
Oct 21, 1999·Methods : a Companion to Methods in Enzymology·G CanzianiI Chaiken

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