Nucleic Acids Research Advance Access originally published online on July 13, 2009
Nucleic Acids Research 2009 37(17):5908-5916; doi:10.1093/nar/gkp586
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Nucleic Acids Research, 2009, Vol. 37, No. 17 5908-5916
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Structural Biology |
Crystal structure of DNA gyrase B' domain sheds lights on the mechanism for T-segment navigation
1National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, 2Graduate University of Chinese Academy of Sciences, Beijing 100039, 3State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, People's Republic of China and 4Center of Structural Biochemistry, Department of Biosciences and Nutrition, Karolinska Institutet, NOVUM 141 57 Huddinge, Sweden
*To whom correspondence should be addressed. Tel/Fax: +86 10 64888464; Email: blj{at}sun5.ibp.ac.cn Correspondence may also be addressed to Da-Cheng Wang. Tel: +86 10 64888547; Fax: +86 10 64888560; Email: dcwang{at}ibp.ac.cn
Received April 7, 2009. Revised June 15, 2009. Accepted June 25, 2009.
DNA gyrase is an indispensible marvelous molecular machine in manipulating the DNA topology for the prokaryotes. In the ‘two-gate’ mechanism of DNA topoisomerase, T-segment navigation from N- to DNA-gate is a critical step, but the structural basis supporting this scheme is unclear. The crystal structure of DNA gyrase B' subfragment from Mycobacterium tuberculosis reveals an intrinsic homodimer. The two subunits, each consisting of a Tail and a Toprim domain, are tightly packed one another to form a ‘crab-like’ organization never observed previously from yeast topo II. Structural comparisons show two orientational alterations of the Tail domain, which may be dominated by a 43-residue peptide at the B' module C-terminus. A highly conserved pentapeptide mediates large-scale intrasubunit conformational change as a hinge point. Mutational studies highlight the significant roles of a negatively charge cluster on a groove at dimer interface. On the basis of structural analysis and mutation experiments, a sluice-like model for T-segment transport is proposed.