Please use this identifier to cite or link to this item: http://lib.jncasr.ac.in:8080/jspui/handle/10572/2472
Title: A Histidine Aspartate Ionic Lock Gates the Iron Passage in Miniferritins from Mycobacterium smegmatis
Authors: Williams, Sunanda Margrett
Chandran, Anu V.
Vijayabaskar, Mahalingam S.
Roy, Sourav
Balaram, Hemalatha
Vishveshwara, Saraswathi
Vijayan, Mamannamana
Chatterji, Dipankar
Keywords: Biochemistry & Molecular Biology
DNA-Binding Protein
Ion Channels
Iron
Mycobacterium
X-Ray Crystallography
Mycobacterium Smegmatis
Ionic Cluster
Iron Oxidation
DNA-Binding Protein
Coli RNA-Polymerase
Escherichia-Coli
Crystal-Structure
Listeria-Innocua
Oxidative Stress
Deinococcus-Radiodurans
Streptococcus-Suis
Bacillus-Anthracis
Hydrogen-Peroxide
Issue Date: 2014
Publisher: American Society Biochemistry Molecular Biology Inc
Citation: Williams, SM; Chandran, AV; Vijayabaskar, MS; Roy, S; Balaram, H; Vishveshwara, S; Vijayan, M; Chatterji, D, A Histidine Aspartate Ionic Lock Gates the Iron Passage in Miniferritins from Mycobacterium smegmatis. Journal of Biological Chemistry 2014, 289 (16) 11042-11058, http://dx.doi.org/10.1074/jbc.M113.524421
Journal of Biological Chemistry
289
16
Abstract: Background: DNA-binding protein from starved cells (Dps) are nano-compartments that can oxidize and store iron rendering protection from free radicals. Results: A histidine-aspartate ionic cluster in mycobaterial Dps2 modulates the rate of iron entry and exit in these proteins. Conclusion: Substitutions that disrupt the cluster interface alter the iron uptake/release properties with localized structural changes. Significance: Identifying important gating residues can help in designing nano-delivery vehicles. 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 for the various mutants to compare structural alterations vis a 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.
Description: Restricted Access
URI: http://hdl.handle.net/10572/2472
ISSN: 0021-9258
Appears in Collections:Research Papers (Hemalatha Balaram)

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