This Article Figures Only Full Text Full Text (PDF) Supporting Information Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My File Cabinet Download to citation manager Request Copyright Permission Citing Articles Citing Articles via CrossRef Google Scholar Articles by Nam, T.-W. Articles by Cha, S.-S. PubMed PubMed Citation Articles by Nam, T.-W. Articles by Cha, S.-S. Social Bookmarking                What's this?

 Previous Article  | Table of Contents |  Next Article 

BIOLOGICAL SCIENCES / BIOCHEMISTRY
Analyses of Mlc–IIB^Glc interaction and a plausible molecular mechanism of Mlc inactivation by membrane sequestration

Tae-Wook Nam^*, Ha Il Jung^,, Young Jun An^,, Young-Ha Park^*, Sang Hee Lee, Yeong-Jae Seok^*,, and Sun-Shin Cha^,

*Department of Biological Sciences and Institute of Microbiology, Seoul National University, Seoul 151-742, Korea; Marine Biotechnology Center, Korea Ocean Research and Development Institute, Ansan 426-744, Korea; and Department of Biological Sciences, Myongji University, Yongin 449-728, Korea

Edited by Winfried Boos, University of Konstanz, Konstanz, Germany, and accepted by the Editorial Board January 22, 2008 (received for review September 30, 2007)

In Escherichia coli, glucose-dependent transcriptional induction of genes encoding a variety of sugar-metabolizing enzymes and transport systems is mediated by the phosphorylation state-dependent interaction of membrane-bound enzyme IICB^Glc (EIICB^Glc) with the global repressor Mlc. Here we report the crystal structure of a tetrameric Mlc in a complex with four molecules of enzyme IIB^Glc (EIIB), the cytoplasmic domain of EIICB^Glc. Each monomer of Mlc has one bound EIIB molecule, indicating the 1:1 stoichiometry. The detailed view of the interface, along with the high-resolution structure of EIIB containing a sulfate ion at the phosphorylation site, suggests that the phosphorylation-induced steric hindrance and disturbance of polar intermolecular interactions impede complex formation. Furthermore, we reveal that Mlc possesses a built-in flexibility for the structural adaptation to its target DNA and that interaction of Mlc with EIIB fused only to dimeric proteins resulted in the loss of its DNA binding ability, suggesting that flexibility of the Mlc structure is indispensable for its DNA binding.

enzyme IICB^Glc | glucose signaling | protein–protein interaction | transcription regulation

The authors declare no conflict of interest.

This article is a PNAS Direct Submission. W.B. is a guest editor invited by the Editorial Board.

Data deposition: The atomic coordinates of the Mlc/EIIB complex and the S-EIIB protein have been deposited in the Protein Data Bank, www.pdb.org (PDB ID codes 3BP8 and 3BP3, respectively).

This article contains supporting information online at www.pnas.org/cgi/content/full/0709295105/DC1.

^¶ Very recently, the C-terminal amino acid (Gly406) of Mlc has been revealed to be involved in interacting with EIIB (26), which gives experimental support to our observation.

To whom correspondence may be addressed. E-mail: yjseok{at}snu.ac.kr or chajung{at}kordi.re.kr

© 2008 by The National Academy of Sciences of the USA

CiteULike    Complore    Connotea    Del.icio.us    Digg    What's this?

Current Issue | Archives | Online Submission | Info for Authors | Editorial Board | About Subscribe | Advertise | Contact | Site Map Copyright © 2008 by the National Academy of Sciences