Journal article
Coiled coil miniprotein randomization on phage leads to charge pattern mimicry of the receptor recognition determinant of interleukin 5
Journal of molecular recognition, v 15(1), pp 33-43
Jan 2002
PMID: 11870920
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Phage display was used to identify sequences that mimic structural determinants in interleukin5 (IL5) for IL5 receptor recognition. A coiled coil stem loop (CCSL) miniprotein scaffold library was constructed with its turn region randomized and panned for binding variants against human IL5 receptor alpha chain (IL5Ralpha). Competition enzyme-linked immunosorbent assays identified CCSL-phage selectants for which binding to IL5Ralpha was competed by IL5. The most frequently selected and IL5-competed CCSL-phage contain charged residues Arg and Glu in their turn sequences, in this regard resembling a beta strand sequence in the 'CD turn' region, of IL5, that has been proposed to present a key determinant for IL5 receptor alpha chain recognition. The most dominant CCSL-phage selectant sequence, PVEGRV, contains a negative/positive charge pattern similar to that seen in the original CD turn. To test the relatedness of CCSL-phage selectant sequences to the IL5 receptor recognition epitope, PVEGRV was grafted into the sequence 87--92 of a monomeric IL5. The resulting IL5 variant, [(87)PVEGRV(92)]GM1, was able to bind to IL5Ralpha in biosensor assays, to elicit TF-1 cell proliferation and to induce STAT5 phosphorylation in TF-1 cells. The results help discern sequence patterns in the IL5 CD turn region which are key in driving receptor recognition and demonstrate the utility of CCSL miniprotein scaffold phage display to identify local IL5 mimetic sequence arrangements that may ultimately lead to IL5 antagonists.
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Details
- Title
- Coiled coil miniprotein randomization on phage leads to charge pattern mimicry of the receptor recognition determinant of interleukin 5
- Creators
- Chuanzhao Li - University of PennsylvaniaCarmela G Plugariu - University of PennsylvaniaJoanna Bajgier - University of PennsylvaniaJohn R White - New FrontierKristin M Liefer - New FrontierSheng-Jiun Wu - University of PennsylvaniaIrwin Chaiken - University of Pennsylvania
- Publication Details
- Journal of molecular recognition, v 15(1), pp 33-43
- Publisher
- Wiley
- Grant note
- R01 GM 55648 / NIGMS NIH HHS R01 AI 40462 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; Drexel University
- Web of Science ID
- WOS:000174191600006
- Scopus ID
- 2-s2.0-0036006154
- Other Identifier
- 991019520428604721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biophysics