Reengineering granulocyte colony-stimulating factor for enhanced stability.


Abstract

Granulocyte colony-stimulating factor is a long-chain cytokine that has both biological and therapeutic applications. It is involved in the production and maturation of neutrophilic progenitor cells and neutrophils and is administered to stimulate the production of white blood cells to reduce the risk of serious infection in immunocompromised patients. We have reengineered granulocyte colony-stimulating factor to improve the thermodynamic stability of the protein, focusing on enhancing the alpha-helical propensity of residues in the antiparallel 4-helix bundle of the protein. These redesigns resulted in proteins with substantially enhanced stability while retaining wild-type levels of biological activity, measured as the ability of the reengineered proteins to stimulate the proliferation of murine myeloid cells transfected with the granulocyte colony-stimulating factor receptor. Study holds ProTherm entries: 11566, 11567, 11568, 11569, 11570, 11571, 11572, 11573, 11574, 11575, 11576, 11577 Extra Details: cytokine; alpha-helical propensity; 4-helix bundle;,biological activity

Submission Details

ID: gjBTbEyP3

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:42 p.m.

Version: 1

Publication Details
Bishop B;Koay DC;Sartorelli AC;Regan L,J. Biol. Chem. (2001) Reengineering granulocyte colony-stimulating factor for enhanced stability. PMID:11406632
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
98.3 Granulocyte colony-stimulating factor P09919 CSF3_HUMAN
100.0 Granulocyte-macrophage colony-stimulating factor P04141 CSF2_HUMAN
94.4 Granulocyte-macrophage colony-stimulating factor Q0MUT8 CSF2_CHLAE