Transcription-repair coupling factor
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<StructureSection load='' size='350' side='right' scene='2eyq/Domainscolorsflabe/3' caption=''> | <StructureSection load='' size='350' side='right' scene='2eyq/Domainscolorsflabe/3' caption=''> | ||
| - | The initial 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. |
When <scene name='46/460252/Mfd_rnap_l1/1'>Mfd binds to a stalled RNA polymerase</scene>, 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. | When <scene name='46/460252/Mfd_rnap_l1/1'>Mfd binds to a stalled RNA polymerase</scene>, 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. | ||
Revision as of 16:17, 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.
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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Proteopedia Page Contributors and Editors (what is this?)
Karsten Theis, Michal Harel, Alexander Berchansky, Wayne Decatur
