IMR Press / FBE / Volume 7 / Issue 3 / DOI: 10.2741/E741

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Mechanisms of PDGFRalpha promiscuity and PDGFRbeta specificity in association with PDGFB
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1 Departamento de Nutricion y Bioquimica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogota D.C., Colombia. Carrera 7ª # 43-82, Carlos Ortiz Bldg, S. J.
2 King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Jeddah, Saudi Arabia 21589
3 GALLY International Biomedical Research Consulting LLC., 7733 Louis Pasteur Drive, #330, San Antonio, TX, USA 78229
4 School of Health Science and Healthcare Administration, University of Atlanta, E. Johns Crossing, #175, Johns Creek, GA, USA 30097

*Author to whom correspondence should be addressed.


Front. Biosci. (Elite Ed) 2015, 7(3), 434–446;
Published: 1 June 2015

Platelet-derived growth factor receptor alpha (PDGFRalpha) interacts with PDGFs A, B, C and AB, while PDGFRbeta binds to PDGFs B and D, thus suggesting that PDGFRalpha is more promiscuous than PDGFRbeta. The structural analysis of PDGFRalpha-PDGFA and PDGFRalpha-PDGFB complexes, and a molecular explanation for the promiscuity of PDGFRalpha and the specificity of PDGFRbeta remain unclear. In the present study, we modeled the three extracellular domains of PDGFRalpha using a previous crystallographic structure of PDGFRbeta as a template. Additionally, we analyzed the interacting residues of PDGFRalpha-PDGFA and PDGFRalpha-PDGFB complexes using docking simulations. The validation of the resulting complexes was evaluated by molecular dynamics simulations. Our results show that that changes of non-aromatic amino acids in PDGFRalpha to aromatic amino acids in PDGFRbeta (I139F, P267F and N204Y) may be involved in the promiscuity of PDGFRalpha. These results may be used as an input for a better peptide design targeting diseases related with the malfunction of PDGF system such as cancer and atherosclerosis.

Molecular Modeling
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