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- Title
Homology Modeling of an Alternative Splice Variant of Human Granulocyte Colony-Stimulating Factor, G-CSF Isoform D, and Study of Its Binding Properties by Molecular Docking.
- Authors
Toghraie, Fatemeh Sadat; Ghaderi, Abbas; Ramezani, Amin
- Abstract
Granulocyte colony-stimulating factor (G-CSF) is known as the major mediator of granulopoiesis. However, overexpression of G-CSF has been reported in many tumors and in most cases, it indicates a poor prognosis. In the present study for the first time, we reported expression of a shorter splice variant of G-CSF with deletion of exon three (G-CSF isoform D) in a G-CSF producing cell line (Mehr 80). Exon skipping can lead to structural and functional changes in the resultant protein. We used "in silico" homology modeling technique to elucidate the 3D structure and physicochemical properties of G-CSF isoform D. Homology modeling was performed by using X-ray crystal structure of full-length G-CSF (PDB ID 1CD9 chain A) as the template. The quality and reliability of model were further assessed by Ramachandran plot, ProSA-web, Verify3D, and ERRAT. To predict the binding modes of G-CSF isoform D to G-CSF receptor, we used docking server SwarmDock. The results of this study revealed that G-CSF isoform D consists of three major helices and a short helix within a connecting loop. All three major helices of isoform D interact with cytokine receptor homology (CRH) domain of the G-CSF receptor. However, G-CSF isoform D may not have proliferative activity since it lacks the binding site for Ig domain of G-CSF receptor. Currently, there is limited information about the G-CSF isoform D. The result of this study would give better insight into the structural and functional properties of this splice variant of G-CSF.
- Subjects
MOLECULAR docking; HOMOLOGY (Biology); CYTOKINE receptors; RNA splicing; GRANULOCYTES; BINDING sites
- Publication
International Journal of Peptide Research & Therapeutics, 2020, Vol 26, Issue 1, p43
- ISSN
1573-3149
- Publication type
Article
- DOI
10.1007/s10989-019-09814-6