title: Alternative binding modes of l-histidine guided by metal ions for the activation of the antiterminator protein HutP of Bacillus subtilis.
abstract: Anti-terminator proteins control gene expression by recognizing control signals within cognate transcripts and then preventing transcription termination. HutP is such a regulatory protein that regulates the expression of the histidine utilization (hut) operon in Bacillus subtilis by binding to cis-acting regulatory sequences in hut mRNAs. During the anti-termination process, l-histidine and a divalent ion are required for hutP to bind to the specific sequence within the hut mRNA. Our previous crystal structure of the HutP-l-histidine-Mg(2+)-RNA ternary complex demonstrated that the l-histidine ligand and Mg(2+) bind together such that the backbone nitrogen and carboxyl oxygen of l-histidine coordinate with Mg(2+). In addition to the Mg(2+), other divalent ions are also known to efficiently support the l-histidine-dependent anti-termination of the hut operon, and the best divalent ion is Zn(2+). In this study, we determined the crystal structure of the HutP-l-histidine-Zn(2+) complex and found that the orientation of l-histidine coordinated to Zn(2+) is reversed relative to that of l-histidine coordinated to Mg(2+), i.e., the imidazole side chain nitrogen of l-histidine coordinates to Zn(2+). This alternative binding mode of the l-histidine ligand to a divalent ion provides further insight into the mechanisms responsible for the activation of RNA binding during the hut anti-termination process.
authors.affiliation: RNA Processing Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Central-6, 1-1-1 Higashi, Tsukuba 305-8566, Japan.
authors.forename: Balasundaresan
authors.initials: B
authors.lastname: Dhakshnamoorthy
authors.affiliation: RNA Processing Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Central-6, 1-1-1 Higashi, Tsukuba 305-8566, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizuno
authors.affiliation: RNA Processing Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Central-6, 1-1-1 Higashi, Tsukuba 305-8566, Japan. Electronic address: pkr-kumar@aist.go.jp.
authors.forename: Penmetcha K R
authors.initials: PKR
authors.lastname: Kumar
mesh_terms: D001412:Bacillus subtilis; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D056831:Coordination Complexes / Q000737:chemistry; D018360:Crystallography, X-Ray; D006639:Histidine / Q000737:chemistry*; D008958:Models, Molecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012329:RNA, Bacterial / Q000737:chemistry; D016601:RNA-Binding Proteins / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
chemical_list: D001426:Bacterial Proteins; D056831:Coordination Complexes; D012329:RNA, Bacterial; D016601:RNA-Binding Proteins; C064872:antiterminator proteins, Bacteria; D006639:Histidine; D015032:Zinc
keywords: Antitermination; Coordination; HutP; Mg(2+); Zn(2+); l-Histidine