title: Molecular basis of the structural stability of hemochromatosis factor E: A combined molecular dynamic simulation and GdmCl-induced denaturation study.
abstract: Hemochromatosis factor E (HFE) is a member of class I MHC family and plays a significant role in the iron homeostasis. Denaturation of HFE induced by guanidinium chloride (GdmCl) was measured by monitoring changes in [θ]222 (mean residue ellipticity at 222 nm), intrinsic fluorescence emission intensity at 346 nm (F346 ) and the difference absorption coefficient at 287 nm (Δε287) at pH 8.0 and 25°C. Coincidence of denaturation curves of these optical properties suggests that GdmCl-induced denaturation (native (N) state ↔ denatured (D) state) is a two-state process. The GdmCl-induced denaturation was found reversible in the entire concentration range of the denaturant. All denaturation curves were analyzed for ΔGD0, Gibbs free energy change associated with the denaturation equilibrium (N state ↔ D state) in the absence of GdmCl, which is a measure of HFE stability. We further performed molecular dynamics simulation for 40 ns to see the effect of GdmCl on the structural stability of HFE. A well defined correlation was established between in vitro and in silico studies.
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
authors.forename: Parvez
authors.initials: P
authors.lastname: Khan
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
authors.forename: Amresh
authors.initials: A
authors.lastname: Parkash
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
authors.forename: Asimul
authors.initials: A
authors.lastname: Islam
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
authors.forename: Faizan
authors.initials: F
authors.lastname: Ahmad
authors.affiliation: Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi, 110025, India.
authors.forename: Md Imtaiyaz
authors.initials: MI
authors.lastname: Hassan
mesh_terms: D002942:Circular Dichroism; D019791:Guanidine / Q000737:chemistry*; D006432:Hemochromatosis / Q000378:metabolism*; D000071020:Hemochromatosis Protein / Q000737:chemistry*; D006801:Humans; D056004:Molecular Dynamics Simulation; D011489:Protein Denaturation; D013050:Spectrometry, Fluorescence
chemical_list: C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D019791:Guanidine
keywords: GdmCl-induced denaturation; hemochromatosis factor E; molecular dynamics simulation; protein folding; protein stability; two-state denaturation