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X-ray structure of Dps from Mycobacterium smegmatisX-ray structure of Dps from Mycobacterium smegmatis
Structural highlights
FunctionDPS_MYCSM Protects DNA from oxidative damage by sequestering intracellular Fe(2+) ion and storing it in the form of Fe(3+) oxyhydroxide mineral. One hydrogen peroxide oxidizes two Fe(2+) ions, which prevents hydroxyl radical production by the Fenton reaction (By similarity). It protects DNA from hydroxyl radical-mediated cleavage. Binds DNA with no apparent sequence specificity without self-aggregation nor promotion of DNA condensation. Is unable to protect DNA from DNase-mediated cleavage.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe structure and function of Mycobacterium smegmatis Dps (DNA-binding proteins from starved cells) and of the protein studied by Gupta and Chatterji, in which the C terminus that is used for binding DNA contains a histidine tag, have been characterized in parallel. The native dodecamer dissociated reversibly into dimers above pH 7.5 and below pH 6.0, with apparent pK(a) values of approximately 7.65 and 4.75; at pH approximately 4.0, dimers formed monomers. Based on structural analysis, the two dissociation steps have been attributed to breakage of the salt bridges between Glu(157) and Arg(99) located at the 3-fold symmetry axes and to protonation of Asp(66) hydrogen-bonded to Lys(36) across the dimer interface, respectively. The C-terminal tag did not affect subunit dissociation, but altered DNA binding dramatically. At neutral pH, protonation of the histidine tag promoted DNA condensation, whereas in the native C terminus, compensation of negative and positive charges led to DNA binding without condensation. This different mode of interaction with DNA has important functional consequences as indicated by the failure of the native protein to protect DNA from DNase-mediated cleavage and by the efficiency of the tagged protein in doing so as a result of DNA sequestration in the condensates. Chemical protection of DNA from oxidative damage is realized by Dps proteins in a multistep iron oxidation/uptake/mineralization process. Dimers have a decreased protection efficiency due to disruption of the dodecamer internal cavity, where iron is deposited and mineralized after oxidation at the ferroxidase center. Reassessment of protein stability, DNA binding, and protection of Mycobacterium smegmatis Dps.,Ceci P, Ilari A, Falvo E, Giangiacomo L, Chiancone E J Biol Chem. 2005 Oct 14;280(41):34776-85. Epub 2005 Jul 19. PMID:16030020[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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