Transcription-repair coupling factor

The shows the domains of Mfd in the conformation of the apo-enzyme. The UvrA interaction site (on domain 2) is occluded by domain 7. The translocase domains (domain 5 and domain 6), through interactions with domains 1 and 3, are locked in an inactive conformation, preventing the typical hinge motion of translocases when they bind and hydrolyze ATP while moving along DNA.

When , the interaction of the RID (domain 4) with RNA polymerase, combined with interactions of domains 5 and domain 6 with DNA and binding to ATP lead to conformational changes that disrupt inter-domain interactions seen in the apo-structure and activate the translocase activity of Mfd. The structures of several intermediates in this process were determined using cryo-EM, shedding light on the activation mechanism, and how translocation of Mfd on DNA leads to disruption of the RNAP elongation complex and recruitment of UvrA.

^[2].

References=

1. ↑ Selby CP. Mfd Protein and Transcription-Repair Coupling in Escherichia coli. Photochem Photobiol. 2017 Jan;93(1):280-295. doi: 10.1111/php.12675. Epub 2017, Jan 18. PMID:27864884 doi:http://dx.doi.org/10.1111/php.12675
2. ↑ Deaconescu AM, Chambers AL, Smith AJ, Nickels BE, Hochschild A, Savery NJ, Darst SA. Structural basis for bacterial transcription-coupled DNA repair. Cell. 2006 Feb 10;124(3):507-20. PMID:16469698 doi:10.1016/j.cell.2005.11.045

3D Structures of Transcription-repair coupling factor

Updated on 15-August-2021

2eyq – EcTRCF – Escherichia coli

6X2N, 6X2F, 6X26, 6X50, 6X43, 6X4W, 6X4Y - EcTRCF, RNA polymerase, RNA, DNA (Cryo EM) /> 3hjh – EcTRCF residues 1-470
2b2n - EcTRCF residues 1-333
6yhz - EcTRCF residues 472-547 – NMR
4dfc – EcTRCF D2 domain 127-213 + UvrABC system protein A
6xeo – EcTRCF + DNA – Cryo EM
3mlq – TtTRCF RNA polymerase interacting domain + DNA-directed RNA polymerase subunit β - Thermus thermophilus
6m6a – TtTRCF + RNA polymerase – Cryo EM
6m6b – TtTRCF + RNA polymerase + ATP-γ-S – Cryo EM
2qsr – TRCF C terminal – Streptococcus pneumoni
6ac6, 6aca, 6ac8 – MsTRCF – Mycobacterium smegmatis
6acx – MsTRCF + ADP

Reference

• Deaconescu AM, Chambers AL, Smith AJ, Nickels BE, Hochschild A, Savery NJ, Darst SA. Structural basis for bacterial transcription-coupled DNA repair. Cell. 2006 Feb 10;124(3):507-20. PMID:16469698 doi:10.1016/j.cell.2005.11.045

Created with the participation of Wayne Decatur