Noncanonical DNA-binding mode of repressor and its disassembly by antirepressor

Minsik Kim, Hee Jung Kim, Sang Hyeon Son, Hye Jin Yoon, Youngbin Lim, Jong Woo Lee, Yeong Jae Seok, Kyeong Sik Jin, Yeon Gyu Yu, Seong Keun Kim, Sangryeol Ryu, Hyung Ho Lee

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4 Citations (Scopus)

Abstract

DNA-binding repressors are involved in transcriptional repression in many organisms. Disabling a repressor is a crucial step in activating expression of desired genes. Thus, several mechanisms have been identified for the removal of a stably bound repressor (Rep) from the operator. Here, we describe an uncharacterized mechanism of noncanonical DNA binding and induction by a Rep from the temperate Salmonella phage SPC32H; this mechanism was revealed using the crystal structures of homotetrameric Rep (92-198) and a hetero-octameric complex between the Rep and its antirepressor (Ant). The canonical method of inactivating a repressor is through the competitive binding of the antirepressor to the operator-binding site of the repressor; however, these studies revealed several noncanonical features. First, Ant does not compete for the DNA-binding region of Rep. Instead, the tetrameric Ant binds to the C-terminal domains of two asymmetric Rep dimers. Simultaneously, Ant facilitates the binding of the Rep N-terminal domains to Ant, resulting in the release of two Rep dimers from the bound DNA. Second, the dimer pairs of the N-terminal DNA-binding domains originate from different dimers of a Rep tetramer (trans model). This situation is different from that of other canonical Reps, in which two N-terminal DNA-binding domains from the same dimeric unit form a dimer upon DNA binding (cis model). On the basis of these observations, we propose a noncanonical model for the reversible inactivation of a Rep by an Ant.

Original languageEnglish
Pages (from-to)E2480-E2488
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number18
DOIs
Publication statusPublished - 2016 May 3

All Science Journal Classification (ASJC) codes

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    Kim, M., Kim, H. J., Son, S. H., Yoon, H. J., Lim, Y., Lee, J. W., Seok, Y. J., Jin, K. S., Yu, Y. G., Kim, S. K., Ryu, S., & Lee, H. H. (2016). Noncanonical DNA-binding mode of repressor and its disassembly by antirepressor. Proceedings of the National Academy of Sciences of the United States of America, 113(18), E2480-E2488. https://doi.org/10.1073/pnas.1602618113