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

Jun Li; Richard Cook; Michael L. Doyle; Preston Hensley; Dean E. McNulty; Irwin Chaiken

doi:10.1073/pnas.94.13.6694

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

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

Jun Li, Richard Cook, Michael L. Doyle, Preston Hensley, Dean E. McNulty and Irwin Chaiken

Proceedings of the National Academy of Sciences - PNAS, v 94(13), pp 6694-6699

24 Jun 1997

DOI: https://doi.org/10.1073/pnas.94.13.6694

PMID: 9192627

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Abstract

Biological Sciences

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 α 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 α chain recruitment processes and that it is the helical packing of the monomeric four-helix bundle unit in IL-5, rather than the helical connectivity itself, that appears to play the major role in presenting structural epitopes to trigger functional receptor activation.

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Title: Monomeric isomers of human interleukin 5 show that 1:1 receptor recruitment is sufficient for function
Creators: Jun Li - New Frontier
Richard Cook
Michael L. Doyle
Preston Hensley
Dean E. McNulty
Irwin Chaiken
Publication Details: Proceedings of the National Academy of Sciences - PNAS, v 94(13), pp 6694-6699
Publisher: The National Academy of Sciences of the USA
Resource Type: Journal article
Language: English
Academic Unit: Biochemistry and Molecular Biology; Drexel University
Web of Science ID: WOS:A1997XH03400021
Scopus ID: 2-s2.0-0030989164
Other Identifier: 991019520428304721

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Collaboration types: Industry collaboration; Domestic collaboration
Web of Science research areas: Biochemistry & Molecular Biology