Transcription in Bacteria
Our lab focuses on the molecular mechanism of bacterial transcription and bacterial transcription regulation. We also develop new bactericidal antibiotics targeting bacterial RNA polymerase. We employ multiple approaches in Structure biology (X-ray crystallography and cryo-EM), Biochemistry, Enzymology, Microbiology, and Bioinformatics. Our current projects include:
Transcription regulation by alternative initiator “sigma” factors
During transcription initiation, bacterial RNAP forms the holoenzyme with a 𝜎 factor to recognize promoter DNA and initiate transcription. We determined the first structure of Mycobacterium tuberculosis (Mtb) RNAP in complex with an Extra-Cytoplasmic Function (ECF) 𝜎 factor--𝜎H, and the first structure of Mtb transcription initiation complex comprising 𝜎H. The structures together reveal the interactions between 𝜎H and RNAP that are essential for 𝜎H-RNAP holoenzyme assembly as well as the interactions between 𝜎H-RNAP and promoter DNA that are responsible for stringent promoter recognition and for promoter unwinding. Our study establishes that ECF σ factors and primary σ factors employ distinct mechanisms for promoter recognition and for promoter unwinding.
Transcription regulation by transcription activators
Transcription initiation is the most-regulated step. Canonical bacterial transcription activators function as dimers and bind to non-transcribed promoter elements to increase transcription of their target genes. Here we provided structural insights into the unique mechanism of transcription activation by Caulobacter crescentus GcrA. We present crystal structures of the C-terminal, factor-interacting domain (GcrA-SID) in complex with domain 2 of 𝜎70, and the N- terminal, DNA-binding domain (GcrA-DBD) in complex with methylated double-stranded DNA (dsDNA). The structures support a mechanism of transcription activation in which GcrA associates with RNA polymerase (RNAP) prior to promoter binding through GcrA-SID, arming RNAP with a flexible GcrA-DBD. The RNAP–GcrA complex then binds and activates target promoters harboring a methylated GcrA binding site either upstream or downstream of the transcription start site.
Transcription in plants
Transcription regulation in plants is much more complicated compared that in bacteria. Three types of RNAPs coexist in an Arabidopsis thaliana cell--three phage-like, single-subunit RNAPs in the mitochondria and chloroplast, a bacteria-like multi-subunit RNAP in the chloroplast, and five eukaryotic RNAP in the nucleus. We are interested in how these RNAPs work and how they are regulated.
Catalytic mechanism of metabolic enzymes
In collaboration with various groups, we are interested in the structure, function, and catalytic mechanism of enzymes responsible for producing primary or secondary metabolites.
A surprising link between
ACS and cAMP
In collaboration with Guoping Zhao's laboratory, we discovered that cAMP is able to inhibit the activity of a central enzyme--acetyl-CoA synthetase.
The Zhang Lab
| CAS Key Laboratory of Synthetic Biology | CAS Center for Excellence in Molecular Plant Sciences |
300 Fenglin Rd. Shanghai, China