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1u8r

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Crystal Structure of an IdeR-DNA Complex Reveals a Conformational Change in Activated IdeR for Base-specific Interactions

Structural highlights

1u8r is a 12 chain structure with sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.75Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IDER_MYCTU Metal-dependent DNA-binding protein that controls transcription of many genes involved in iron metabolism. Acts as a repressor of siderophore biosynthesis and as a positive modulator of iron storage. Also regulates expression of transporters, proteins involved in siderophore synthesis, iron storage and transcriptional regulators.^[1] ^[2]

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 PubMed

The iron-dependent regulator (IdeR) is an essential protein in Mycobacterium tuberculosis that regulates iron uptake in this major pathogen. Under high iron concentrations, IdeR binds to several operator regions and represses transcription of target genes. Here, we report the first crystal structure of cobalt-activated IdeR bound to the mbtA-mbtB operator at 2.75 A resolution. IdeR binds to the DNA as a "double-dimer" complex with two dimers on opposite sides of the DNA duplex with the dimer axes deviating approximately 157 degrees. The asymmetric unit contains two such double-dimer complexes with a total molecular mass of 240 kDa. Two metal-binding sites are fully occupied with the SH3-like third domain adopting a "wedge" position to interact with the two other domains, and providing two ligands for the metal site 1 in all eight subunits per asymmetric unit. A putative sodium ion is observed to mediate interactions between Asp35 and DNA. There is a conformational change in the DNA-binding domain caused by a 6-9 degrees rotation of the helix-turn-helix motif with respect to the rest of the molecule upon binding to the DNA. Ser37 and Pro39 make specific interactions with conserved thymine bases while Gln43 makes non-specific contacts with different types of bases in different subunits. A "p1s2C3T4a5" base recognition pattern is proposed to be the basis for key interactions for each IdeR subunit with the DNA in the IdeR-DNA complex structure.

Crystal structure of an IdeR-DNA complex reveals a conformational change in activated IdeR for base-specific interactions.,Wisedchaisri G, Holmes RK, Hol WG J Mol Biol. 2004 Sep 24;342(4):1155-69. PMID:15351642^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Gold B, Rodriguez GM, Marras SA, Pentecost M, Smith I. The Mycobacterium tuberculosis IdeR is a dual functional regulator that controls transcription of genes involved in iron acquisition, iron storage and survival in macrophages. Mol Microbiol. 2001 Nov;42(3):851-65. PMID:11722747
↑ Rodriguez GM, Voskuil MI, Gold B, Schoolnik GK, Smith I. ideR, An essential gene in mycobacterium tuberculosis: role of IdeR in iron-dependent gene expression, iron metabolism, and oxidative stress response. Infect Immun. 2002 Jul;70(7):3371-81. PMID:12065475
↑ Wisedchaisri G, Holmes RK, Hol WG. Crystal structure of an IdeR-DNA complex reveals a conformational change in activated IdeR for base-specific interactions. J Mol Biol. 2004 Sep 24;342(4):1155-69. PMID:15351642 doi:10.1016/j.jmb.2004.07.083