Identification of Interfacial Residues Involved in Hepcidin-Ferroportin Interaction
Prasoon Kumar Thakur,
Robert E. Fleming,
Md. Imtaiyaz Hassan.
The interaction of hepcidin (HEPC) and ferroportin (FPN) is an essential event in iron homeostasis. HEPC
binds to FPN, and subsequently degrades it through phosphorylation and ubiquitination. Present work described a computational
study to identify interfacial residues involved in FPN–HEPC interactions. We have predicted three-dimensional
structure of human FPN using homology modeling followed by docking analysis and molecular dynamics simulations.
Our study revealed that FPN has HEPC-binding sites on extracellular loops: ECL4, ECL5 and ECL6. The provided outcome
is consistent with mutagenesis studies on FPN. We have identified several electrostatic interactions between
charged residues Asp325 (ECL4), ECL5 (Glu448) and Glu518 (ECL6) of FPN with residues His3, Arg16, Lys18 of
HEPC, which are essentially important for interfacial contact between them. These results provide an evidence for structural
basis of FPN–HEPC interactions and their future clinical application.
Keywords: Ferroportin, Hepcidin, Structural modulation, Elastic network model, Iron homeostasis.
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