Structural basis of gene regulation by the tetracycline inducible Tet repressor-operator system.
作者： Wolfram Saenger , Winfried Hinrichs , Peter Orth , Dirk Schnappinger , Wolfgang Hillen
DOI: 10.1038/73324
关键词:
摘要: The tetracycline repressor (TetR) regulates the most abundant resistance mechanism against antibiotic in gram-negative bacteria. TetR protein and its mutants are commonly used as control elements to regulate gene expression higher eukaryotes. We present crystal structure of homodimer complex with palindromic DNA operator at 2.5 A resolution. Comparison inducer tetracycline-Mg2+ allows induction be deduced. Inducer binding core initiates conformational changes starting C-terminal unwinding shifting short helix α6 each monomer. This forces a pendulum-like motion α4, which increases separation attached domains by 3 A, abolishing affinity for DNA.
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nature.com参考文章(40)
A. Wissmann, R. Baumeister, G. Müller, B. Hecht, V. Helbl, K. Pfleiderer, W. Hillen, Amino acids determining operator binding specificity in the helix-turn-helix motif of Tn10 Tet repressor. The EMBO Journal. ,vol. 10, pp. 4145- 4152 ,(1991) , 10.1002/J.1460-2075.1991.TB04992.X
Sabine Freundlieb, Udo Baron, Angelika L. Bonin, Manfred Gossen, Hermann Bujard, Use of tetracycline-controlled gene expression systems to study mammalian cell cycle Methods in Enzymology. ,vol. 283, pp. 159- 173 ,(1997) , 10.1016/S0076-6879(97)83014-5
Zbyszek Otwinowski, Wladek Minor, Processing of X-ray diffraction data collected in oscillation mode Methods in Enzymology. ,vol. 276, pp. 307- 326 ,(1997) , 10.1016/S0076-6879(97)76066-X
John WR Schwabe, The role of water in protein-DNA interactions. Current Opinion in Structural Biology. ,vol. 7, pp. 126- 134 ,(1997) , 10.1016/S0959-440X(97)80016-4
T. A. Steitz, D. H. Ohlendorf, D. B. McKay, W. F. Anderson, B. W. Matthews, Structural similarity in the DNA-binding domains of catabolite gene activator and cro repressor proteins Proceedings of the National Academy of Sciences of the United States of America. ,vol. 79, pp. 3097- 3100 ,(1982) , 10.1073/PNAS.79.10.3097
Z. Otwinowski, R. W. Schevitz, R.-G. Zhang, C. L. Lawson, A. Joachimiak, R. Q. Marmorstein, B. F. Luisi, P. B. Sigler, Crystal structure of trp repressor/operator complex at atomic resolution. Nature. ,vol. 335, pp. 321- 329 ,(1988) , 10.1038/335321A0
Christine Heuer, Wolfgang Hillen, Tet repressor-tet operator contacts probed by operator DNA-modification interference studies Journal of Molecular Biology. ,vol. 202, pp. 407- 415 ,(1988) , 10.1016/0022-2836(88)90274-4
Gerhard Müller, Brigitte Hecht, Vera Helbl, Winfried Hinrichs, Wolfram Saenger, Wolfgang Hillen, Characterization of non-inducible Tet repressor mutants suggests conformational changes necessary for induction. Nature Structural & Molecular Biology. ,vol. 2, pp. 693- 703 ,(1995) , 10.1038/NSB0895-693
Michele A Kercher, Ponzy Lu, Mitchell Lewis, Lac repressor-operator complex. Current Opinion in Structural Biology. ,vol. 7, pp. 76- 85 ,(1997) , 10.1016/S0959-440X(97)80010-3
Peter Orth, Claudia Alings, Dirk Schnappinger, Wolfram Saenger, Winfried Hinrichs, Crystallization and preliminary X‐ray analysis of the Tet‐repressor/operator complex Acta Crystallographica Section D-biological Crystallography. ,vol. 54, pp. 99- 100 ,(1998) , 10.1107/S0907444997007646