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.

journal_name

Biopolymers

journal_title

Biopolymers

authors

Khan P,Parkash A,Islam A,Ahmad F,Hassan MI

doi

10.1002/bip.22760

subject

Has Abstract

pub_date

2016-03-01 00:00:00

pages

133-42

issue

3

eissn

0006-3525

issn

1097-0282

journal_volume

105

pub_type

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