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

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

来源：Proceedings of the National Academy of Sciences of the United States of America, 2016, 113(18): E2480-E2488.

DOI：10.1073/pnas.1602618113

• repressor
• antirepressor
• transcription
• Salmonella
• bacteriophage

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.

• 出版日期2016-5-3