H-1, C-13 and N-15 resonance assignments of a highly-soluble murine interleukin-3 analogue with wild-type bioactivity
- Author(s)
- Yao, SG; Murphy, JM; Low, A; Norton, RS;
- Details
- Publication Year 2010-04,Volume 4,Issue #1,Page 73-77
- Journal Title
- BIOMOLECULAR NMR ASSIGNMENTS
- Publication Type
- Journal Article
- Abstract
- Interleukin-3 (IL-3) is a cytokine that acts as a critical mediator of inflammation and immune responses to infections. IL-3, like interleukin-5 (IL-5) and granulocyte-macrophage colony stimulating factor (GM-CSF), exerts its effects on target cells via receptors composed of cytokine-specific alpha-subunits and a common beta-subunit (beta c-subunit, shared with IL-5 and GM-CSF). In contrast to humans, mice also possess an additional beta-receptor, beta(IL-3), that can specifically bind IL-3. Except for a study carried out on an analogue of human IL-3 that contains 14 mutations, structure-related studies of IL-3 have been very limited, largely because of its poor solution behaviour. Here we report H-1, C-13, and N-15 chemical shift assignments of murine IL-3 comprising residues 33-156 (SWISS-PROT accession number: P01586), in which the only mutation is an alanine substitution of Cys105. The mIL-3 construct used in the present study was engineered by eliminating residues 27-32 of the N-terminus (the first 26 residues of the primary sequence of mIL-3 are cleaved in vivo during secretion), the C-terminal 10 residues (157-166), and a disulfide bond between Cys105 and Cys166 that is poorly conserved in orthologue sequences. The new construct vastly improves the solubility of murine IL-3 while maintaining its wild-type biological activity.
- Publisher
- SPRINGER
- Keywords
- SECONDARY STRUCTURE; NMR; VARIANT
- Publisher's Version
- https://doi.org/10.1007/s12104-010-9213-1
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2010-04-01 12:00:00