8TP8

Structure of the C. crescentus WYL-activator, DriD, bound to ssDNA and cognate DNA

Summary for 8TP8

• Entry DOI: 10.2210/pdb8tp8/pdb
• Descriptor: DeoR-family transcriptional regulator, DNA (5'-D(*AP*TP*AP*CP*GP*AP*CP*AP*GP*TP*TP*AP*CP*TP*GP*TP*CP*GP*TP*AP*T)-3'), DNA (5'-D(*AP*TP*AP*CP*GP*AP*CP*AP*GP*TP*AP*AP*CP*TP*GP*TP*CP*GP*TP*AP*T)-3'), ... (6 entities in total)
• Functional Keywords: wyl motif, drid, c. crescentus, dna damage repair, ssdna, transcription activation, transcription, transcription-dna complex, transcription/dna
• Biological source: Caulobacter vibrioides NA1000; More
• Total number of polymer chains: 12
• Total formula weight: 182002.44

Authors

Schumacher, M.A. (deposition date: 2023-08-04, release date: 2023-11-29, Last modification date: 2024-03-13)

Primary citation

Schumacher, M.A.,Cannistraci, E.,Salinas, R.,Lloyd, D.,Messner, E.,Gozzi, K.
Structure of the WYL-domain containing transcription activator, DriD, in complex with ssDNA effector and DNA target site.
Nucleic Acids Res., 52:1435-1449, 2024

PubMed Abstract: Transcription regulators play central roles in orchestrating responses to changing environmental conditions. Recently the Caulobacter crescentus transcription activator DriD, which belongs to the newly defined WYL-domain family, was shown to regulate DNA damage responses independent of the canonical SOS pathway. However, the molecular mechanisms by which DriD and other WYL-regulators sense environmental signals and recognize DNA are not well understood. We showed DriD DNA-binding is triggered by its interaction with ssDNA, which is produced during DNA damage. Here we describe the structure of the full-length C. crescentus DriD bound to both target DNA and effector ssDNA. DriD consists of an N-terminal winged-HTH (wHTH) domain, linker region, three-helix bundle, WYL-domain and C-terminal WCX-dimer domain. Strikingly, DriD binds DNA using a novel, asymmetric DNA-binding mechanism that results from different conformations adopted by the linker. Although the linker does not touch DNA, our data show that contacts it makes with the wHTH are key for specific DNA binding. The structure indicates how ssDNA-effector binding to the WYL-domain impacts wHTH DNA binding. In conclusion, we present the first structure of a WYL-activator bound to both effector and target DNA. The structure unveils a unique, asymmetric DNA binding mode that is likely conserved among WYL-activators.

PubMed: 38142455
DOI: 10.1093/nar/gkad1198

Experimental method

X-RAY DIFFRACTION (2.74 Å)