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GM-CSF Receptor Activation

Client: Isabel Romero Calvo, MS, PhD

Audience: Graduate Students

Media: VMD, 3Ds Max, Adobe Photoshop, Illustrator

Purpose: This molecular illustration is intended to educate a biomedical professional or graduate student about the steps to achieve GM-CSF receptor activation. Receptor activation is initiated by the low-affinity interaction between GM-CSF and the alpha subunit that becomes a hexameric complex. GM-CSF structure doesn’t allow “bending legs” between beta chains so the hexameric complex becomes a higher order dodecamer complex. The 3D rendered molecule shows the receptor in its activated stage.

 

Role: Research, 3D Modeling/Resurfacing, Design Strategy, Content Writing, 2D Asset Creation

Sketch

VMD Molecular Model Challenge

All subunits were provided by PDB and manipulated in VMD and 3Ds max. Since the subunits were only provided separately and not as an activated receptor as seen in the illustration, attention to the specific point of molecular interaction were noted and intentionally matched to the best of my abilities.

References

1. Broughton, S. E., Nero, T. L., Dhagat, U., Kan, W. L., Hercus, T. R., Tvorogov, D., Lopez, A. F., & Parker, M. W. (2015). The βc receptor family – Structural insights and their functional implications. Cytokine, 74(2), 247–258. https://doi.org/10.1016/j.cyto.2015.02.005

2. Hercus, T. R., Thomas, D., Guthridge, M. A., Ekert, P. G. et al. (2009). The granulocyte-macrophage colony-stimulating factor receptor: Linking its structure to cell signaling and its role in disease. Blood, 114(7), 1289–1298. https://doi.org/10.1182/blood-2008-12-164004

3. Hercus, T. R., Thomas, D., Guthridge, M. A., Ekert, P. G., King-Scott, J., Parker, M. W., & Lopez, A. F. (2012). The GM-CSF receptor family: Mechanism of activation and implications for disease. Growth factors (Chur, Switzerland), 30(2), 63–75. https://doi.org/10.3109/08977194.2011.649919  

4. Hansen, G., Hercus, T. R., McClure, B. J., Stomski, F. C., Dottore, M., Powell, J., Ramshaw, H., Woodcock, J. M., Xu, Y., Guthridge, M., McKinstry, W. J., Lopez, A. F., & Parker, M. W. (2008). The structure of the GM-CSF receptor complex reveals a distinct mode of cytokine receptor activation. Cell, 134(3), 496–507. https://doi.org/10.1016/j.cell.2008.05.053

5. McGeachy, M. J., Cua, D. J., & Gaffen, S. L. (2019). The IL-17 Family of Cytokines in Health and Disease. Immunity, 50(4), 892–906. https://doi.org/10.1016/j.immuni.2019.03.021


PDB files: α and β chains - 4NKQ; JAK2 - 6E2P

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