Crystal structure of a heat-inducible transcriptional repressor HrcA from Thermotoga maritima: Structural insight into DNA binding and dimerization

Jinyu Liu, Candice Huang, Dong Hae Shin, Hisao Yokota, Jaru Jancarik, Jeong Sun Kim, Paul D. Adams, Rosalind Kim, Sung Hou Kim

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19 Scopus citations


All cells have a defense mechanism against a sudden heat-shock stress. Commonly, they express a set of proteins that protect cellular proteins from being denatured by heat. Among them, GroE and DnaK chaperones are representative defending systems, and their transcription is regulated by a heat-shock repressor protein HrcA. HrcA repressor controls the transcription of groE and dnaK operons by binding the palindromic CIRCE element, presumably as a dimer, and the activity of HrcA repressor is modulated by GroE chaperones. Here, we report the first crystal structure of a heat-inducible transcriptional repressor, HrcA, from Thermotoga maritima at 2.2 Å resolution. The Tm_HrcA protein crystallizes as a dimer. The monomer is composed of three domains: an N-terminal winged helix-turn-helix domain (WH), a GAF-like domain, and an inserted dimerizing domain (IDD). The IDD shows a unique structural fold with an anti-parallel β-sheet composed of three β-strands sided by four α-helices. The Tm_HrcA dimer structure is formed through hydrophobic contact between the IDDs and a limited contact that involves conserved residues between the GAF-like domains. In the overall dimer structure, the two WH domains are exposed, but the conformation of these two domains seems to be incompatible with DNA binding. We suggest that our structure may represent an inactive form of the HrcA repressor. Structural implication on how the inactive form of HrcA may be converted to the active form by GroEL binding to a conserved C-terminal sequence region of HrcA is discussed.

Original languageEnglish
Pages (from-to)987-996
Number of pages10
JournalJournal of Molecular Biology
Issue number5
StatePublished - 29 Jul 2005

Bibliographical note

Funding Information:
We thank Barbara Gold for cloning, Marlene Henriquez and Bruno Martinez for expression studies and cell paste preparation, Yun Lou for analytical size-exclusion column experiments, John-Marc Chandonia for bioinformatics search of the gene. We are grateful to the staff at the Advanced Light Source, which is supported by the Director, Office of Science, Office of Basic Energy Sciences, Materials Sciences Division, of the US Department of Energy under Contract no. DE-AC03-76SF00098 at Lawrence Berkeley National Laboratory. Special thanks to Dr Jeong-Sun Kim for helping with the preparation of the manuscript. The work described here was supported by the National Institutes of Health GM 62412, Protein Structure Initiative.


  • Crystal structure
  • GroES/GroEL
  • HrcA
  • Structural genomics


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