Journal article
Mutagenesis in the C-terminal of human interleukin 5 reveals central patch for receptor alpha chain recognition
Proceedings of the National Academy of Sciences - PNAS, Vol.92(24), p10879
21 Nov 1995
Abstract
Cassette mutagenesis was used to identify side chains in human interleukin 5 (hlL-5) that mediate binding to hIL-5 receptor a chain (hlL-5r[alpha]). A series of single alanine substitutions was introduced into a stretch of residues in the C-terminal region, including helix D, which previously had been implicated in receptor a chain recognition and which is aligned on the IL-5 surface so as to allow the topography of receptor binding residues to be examined. hIL-5 and single site mutants were expressed in COS cells, their interactions with hIL-5r[alpha] were measured by a sandwich surface plasmon resonance biosensor method, and their biological activities were measured by an IL-5-dependent cell proliferation assay. A pattern of mutagenesis effects was observed, with greatest impact near the interface between the two four-helix bundles of IL-5, in particular at residues Glu-110 and Trp-111, and least at the distal ends of the D helices. This pattern suggests the possibility that residues near the interface of the two four-helix bundles in hIL-5 comprise a central patch or hot spot, which constitutes an energetically important a chain recognition site. This hypothesis suggests a structural explanation for the 1:1 stoichiometry observed for the complex of hIL-5 with hIL-5R[alpha].
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Details
- Title
- Mutagenesis in the C-terminal of human interleukin 5 reveals central patch for receptor alpha chain recognition
- Creators
- Thomas MortonJun LiRichard CookIrwin Chaiken
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.92(24), p10879
- Publisher
- National Academy of Sciences
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Drexel University
- Identifiers
- 991019520416604721