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PDBsum entry 4m32
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DNA binding protein
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PDB id
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4m32
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References listed in PDB file
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Key reference
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Title
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A histidine aspartate ionic lock gates the iron passage in miniferritins from mycobacterium smegmatis.
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Authors
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S.M.Williams,
A.V.Chandran,
M.S.Vijayabaskar,
S.Roy,
H.Balaram,
S.Vishveshwara,
M.Vijayan,
D.Chatterji.
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Ref.
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J Biol Chem, 2014,
289,
11042-11058.
[DOI no: ]
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PubMed id
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Abstract
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Dps (DNA-binding protein from starved cells) are dodecameric assemblies
belonging to the ferritin family that can bind DNA, carry out ferroxidation, and
store iron in their shells. The ferritin-like trimeric pore harbors the channel
for the entry and exit of iron. By representing the structure of Dps as a
network we have identified a charge-driven interface formed by a histidine
aspartate cluster at the pore interface unique to Mycobacterium smegmatis Dps
protein, MsDps2. Site-directed mutagenesis was employed to generate mutants to
disrupt the charged interactions. Kinetics of iron uptake/release of the wild
type and mutants were compared. Crystal structures were solved at a resolution
of 1.8-2.2 Å for the various mutants to compare structural alterations vis à
vis the wild type protein. The substitutions at the pore interface resulted in
alterations in the side chain conformations leading to an overall weakening of
the interface network, especially in cases of substitutions that alter the
charge at the pore interface. Contrary to earlier findings where conserved
aspartate residues were found crucial for iron release, we propose here that in
the case of MsDps2, it is the interplay of negative-positive potentials at the
pore that enables proper functioning of the protein. In similar studies in
ferritins, negative and positive patches near the iron exit pore were found to
be important in iron uptake/release kinetics. The unique ionic cluster in MsDps2
makes it a suitable candidate to act as nano-delivery vehicle, as these gated
pores can be manipulated to exhibit conformations allowing for slow or fast
rates of iron release.
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