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Transcription-repair coupling factor
From Proteopedia
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<StructureSection load='' size='350' side='right' scene='2eyq/Domainscolorsflabe/3' caption=''> | <StructureSection load='' size='350' side='right' scene='2eyq/Domainscolorsflabe/3' caption=''> | ||
The <scene name='2eyq/Domainscolorsflabe/3'>initial scene</scene> 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. | The <scene name='2eyq/Domainscolorsflabe/3'>initial scene</scene> 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. | ||
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When <scene name='46/460252/Mfd_rnap_l1/2'>Mfd binds to a stalled RNA polymerase</scene>, the RID (domain 4) binds to the beta subunit of RNA polymerase and domains 5 and domain 6 bind to DNA and ATP. These multiple binding events require a different relative orientation of RID and the translocase domains, and the necessary conformational changes disrupt inter-domain interactions seen in the apo-structure while activating the translocase activity of Mfd. The structures of several intermediates in the presences of stalled RNAP were determined using cryo-EM, shedding light on the loading and activation mechanism, as well as how translocation of Mfd on DNA leads to disruption of the RNAP elongation complex and recruitment of UvrA.<ref>DOI:10.1016/j.cell.2005.11.045</ref> | When <scene name='46/460252/Mfd_rnap_l1/2'>Mfd binds to a stalled RNA polymerase</scene>, the RID (domain 4) binds to the beta subunit of RNA polymerase and domains 5 and domain 6 bind to DNA and ATP. These multiple binding events require a different relative orientation of RID and the translocase domains, and the necessary conformational changes disrupt inter-domain interactions seen in the apo-structure while activating the translocase activity of Mfd. The structures of several intermediates in the presences of stalled RNAP were determined using cryo-EM, shedding light on the loading and activation mechanism, as well as how translocation of Mfd on DNA leads to disruption of the RNAP elongation complex and recruitment of UvrA.<ref>DOI:10.1016/j.cell.2005.11.045</ref> | ||
Revision as of 17:39, 15 August 2021
The bacterial transcription-repair coupling factor TRCF, also called Mfd translocase, is a DNA repair protein. It has a role in transcription-coupled repair, a subpathway of nucleotide excision repair (NER). Mfd recognizes stalled RNA polymerase (RNAP) and either restarts transcription or removes the stalled polymerase and recruits the NER proteins UvrA and UvrB.
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Function
Mfd has ATP hydrolysis activity, DNA binding sites and a UvrA binding sites. These three functions are inhibited in the isolated enzyme, but are activated when Mfd encounters stalled RNA polymerase (or through various mutations that remove inhibitory domains [1]). Mfd also contains an RNA interaction domain (RID) that binds to the beta subunit of RNAP.
Structural highlights
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References
- ↑ 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
- ↑ 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
Created with the participation of Wayne Decatur
Proteopedia Page Contributors and Editors (what is this?)
Karsten Theis, Michal Harel, Alexander Berchansky, Wayne Decatur
