HTH_3 family

General information

   Bacteriophage lambda C1 repressor controls the expression of viral genes as part of the lysogeny/lytic growth switch. C1 is essential for maintaining lysogeny, where the phage replicates non-disruptively along with the host. If the host cell is threatened, then lytic growth is induced. The Lambda C1 repressor consists of two domains connected by a linker: an N-terminal DNA-binding domain that also mediates interactions with RNA polymerase, and a C-terminal dimerisation domain [1]. The DNA-binding domain consists of four helices in a closed folded leaf motif. Several different phage repressors from different helix-turn-helix families contain DNA-binding domains that adopt a similar topology. These include the Lambda Cro repressor, Bacteriophage 434 C1 and Cro repressors, P22 C2 repressor, and Bacteriophage Mu Ner protein.
   The DNA-binding domain of Bacillus subtilis spore inhibition repressor SinR is identical to that of phage repressors [2]. SinR represses sporulation, which only occurs in response to adverse conditions. This provides a possible evolutionary link between the two adaptive responses of bacterial sporulation and prophage induction.
   Other DNA-binding domains also display similar structural folds to that of Lambda C1. These include bacterial regulators such as the purine repressor (PurR), the lactose repressor (Lacr) and the fructose repressor (FruR), each of which has an N-terminal DNA-binding domain that exhibits a fold similar to that of lambda C1, except that they lack the first helix [3, 4, 5]. POU-specific domains found in transcription factors such as in Oct-1, Pit-1 and Hepatocyte nuclear factor 1a (LFB1/HNF1) display four-helical fold DNA-binding domains similar to that of Lambda C1 [6, 7, 8]. The N-terminal domain of cyanase has an alpha-helix bundle motif similar to Lambda C1, but it probably does not bind DNA. Cyanase is an enzyme found in bacteria and plants that catalyses the reaction of cyanate with bicarbonate to produce ammonia and carbon dioxide in response to extracellular cyanate [9].

1. Bell C.E. , Frescura P. , Hochschild A. , Lewis M. Crystal structure of the lambda repressor C-terminal domain provides a model for cooperative operator binding. Cell 101 801-811 2000 [PubMed: 10892750]
2. Lewis R.J. , Brannigan J.A. , Offen W.A. , Smith I. , Wilkinson A.J. An evolutionary link between sporulation and prophage induction in the structure of a repressor:anti-repressor complex. J. Mol. Biol. 283 907-912 1998 [PubMed: 9799632]
3. Schumacher M.A. , Choi K.Y. , Zalkin H. , Brennan R.G. Crystal structure of LacI member, PurR, bound to DNA: minor groove binding by alpha helices. Science 266 763-770 1994 [PubMed: 7973627]
4. Bell C.E. , Lewis M. A closer view of the conformation of the Lac repressor bound to operator. Nat. Struct. Biol. 7 209-214 2000 [PubMed: 10700279]
5. Penin F. , Geourjon C. , Montserret R. , Bockmann A. , Lesage A. , Yang Y.S. , Bonod-bidaud C. , Cortay J.C. , Negre D. , Cozzone A.J. , Deleage G. Three-dimensional structure of the DNA-binding domain of the fructose repressor from Escherichia coli by 1H and 15N NMR. J. Mol. Biol. 270 496-510 1997 [PubMed: 9237914]
6. Remenyi A. , Tomilin A. , Pohl E. , Lins K. , Philippsen A. , Reinbold R. , Scholer H.R. , Wilmanns M. Differential dimer activities of the transcription factor Oct-1 by DNA-induced interface swapping. Mol. Cell 8 569-580 2001 [PubMed: 11583619]
7. Jacobson E.M. , Li P. , Leon-del-Rio A. , Rosenfeld M.G. , Aggarwal A.K. Structure of Pit-1 POU domain bound to DNA as a dimer: unexpected arrangement and flexibility. Genes Dev. 11 198-212 1997 [PubMed: 9009203]
8. Chi Y.I. , Frantz J.D. , Oh B.C. , Hansen L. , Dhe-Paganon S. , Shoelson S.E. Diabetes mutations delineate an atypical POU domain in HNF-1alpha. Mol. Cell 10 1129-1137 2002 [PubMed: 12453420]
9. Walsh M.A. , Otwinowski Z. , Perrakis A. , Anderson P.M. , Joachimiak A. Structure of cyanase reveals that a novel dimeric and decameric arrangement of subunits is required for formation of the enzyme active site. Structure 8 505-514 2000 [PubMed: 10801492]