Prasoon Kumar Thakur1, Vishrant Tyagi2, Faizan Ahmad2, Md. Imtaiyaz Hassan2
1Department of Computer Science, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
2Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India.
ABSTRACT
Hepcidin is a 25 amino-acid long peptide hormone, possesses antimicrobial activity. A mutation in hepcidin has been linked to iron deficiency, anemia and iron overload hemochromatosis. Ferroportin (FPN), an iron exporter binds to the hepcidin and subsequently internalized and degraded, leading to decreased export of cellular iron. Here we are reporting three-dimensional structure of the human FPN, calculated by comparative modeling. Structure of FPN is purely a-helical, showing many transmembrane helices. In order to understand the role of hepcidin in iron homeostasis, we studied the binding of hepcidin to FPN in silico. The FPN was used for docking to the hepcidin, which fitted well in hepcidin binding domain of FPN. The binding energy of hepcidin- FPN docked complex was found to be -6.40763199 kcal/mol and configuration entropy was found in the range of ~ 5-15 kcal/mol. This binding energy suggested that this complex is quiet stable. There are sufficient numbers of interaction formed reflects their strong and specific binding. Our results provide a structural evidence for the role of hepcidin in the systemic regulation of FPN expression in vivo. Furthermore, it provides an insight for a new therapeutic approach for using synthetic hepcidin, FPN antagonists to correct the iron homeostasis. Read more…
