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 PDB Entries

Structure ID Release Date Resolution Structure Title
1CD9 1999-03-08T00:00:00+0000 2.8 2:2 COMPLEX OF G-CSF WITH ITS RECEPTOR
1GNC 1994-03-08T00:00:00+0000 0 STRUCTURE AND DYNAMICS OF THE HUMAN GRANULOCYTE COLONY-STIMULATING FACTOR DETERMINED BY NMR SPECTROSCOPY. LOOP MOBILITY IN A FOUR-HELIX-BUNDLE PROTEIN
1PGR 1999-03-08T00:00:00+0000 3.5 2:2 COMPLEX OF G-CSF WITH ITS RECEPTOR
1RHG 1993-01-29T00:00:00+0000 2.2 THE STRUCTURE OF GRANULOCYTE-COLONY-STIMULATING FACTOR AND ITS RELATIONSHIP TO THOSE OF OTHER GROWTH FACTORS
2D9Q 2005-12-12T00:00:00+0000 2.8 Crystal Structure of the Human GCSF-Receptor Signaling Complex
5GW9 2016-09-09T00:00:00+0000 1.65 Crystal structure of C163, a backbone circularized G-CSF
5ZO6 2018-04-12T00:00:00+0000 1.7 Crystal structure of C166, a backbone circularized G-CSF
1CSG 1992-11-23T00:00:00+0000 2.7 Three-dimensional structure of recombinant human granulocyte-macrophage colony-stimulating factor
2GMF 1996-04-24T00:00:00+0000 2.4 HUMAN GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR
4NKQ 2013-11-13T00:00:00+0000 3.3 Structure of a Cytokine Receptor Complex

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