5u8s
From Proteopedia
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==Structure of eukaryotic CMG helicase at a replication fork== | ==Structure of eukaryotic CMG helicase at a replication fork== | ||
| - | <StructureSection load='5u8s' size='340' side='right' caption='[[5u8s]], [[Resolution|resolution]] 6.10Å' scene=''> | + | <StructureSection load='5u8s' size='340' side='right'caption='[[5u8s]], [[Resolution|resolution]] 6.10Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5u8s]] is a 13 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U8S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U8S FirstGlance]. <br> | <table><tr><td colspan='2'>[[5u8s]] is a 13 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U8S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U8S FirstGlance]. <br> | ||
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[[Category: Baker's yeast]] | [[Category: Baker's yeast]] | ||
[[Category: DNA helicase]] | [[Category: DNA helicase]] | ||
| + | [[Category: Large Structures]] | ||
[[Category: Donnell, M E.O]] | [[Category: Donnell, M E.O]] | ||
[[Category: Georgescu, R]] | [[Category: Georgescu, R]] | ||
Revision as of 09:13, 1 January 2020
Structure of eukaryotic CMG helicase at a replication fork
Structural highlights
Function[MCM5_YEAST] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity; specifically the MCM2-MCM5 association is proposed to be reversible and to mediate a open ring conformation which may facilitate DNA loading. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity.[1] [2] [PSF3_YEAST] Functions as part of the GINS complex which plays an essential role in the initiation of DNA replication by binding to DNA replication origins and facilitating the assembly of the DNA replication machinery.[UniProtKB:P40359][3] [MCM3_YEAST] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity. Necessary for cell growth.[4] [5] [MCM6_YEAST] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity. Required for the entry in S phase and for cell division.[6] [7] [PSF2_YEAST] Functions as part of the GINS complex which plays an essential role in the initiation of DNA replication by binding to DNA replication origins and facilitating the assembly of the DNA replication machinery.[8] [MCM2_YEAST] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity; specifically the MCM2-MCM5 association is proposed to be reversible and to mediate a open ring conformation which may facilitate DNA loading. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity. Necessary for cell growth.[9] [10] [PSF1_YEAST] Required for DNA replication. Functions as part of the GINS complex which plays an essential role in the initiation of DNA replication by binding to DNA replication origins and facilitating the assembly of the DNA replication machinery. Required for the chromatin binding of CDC45.[11] [SLD5_YEAST] Required for DNA replication. Functions as part of the GINS complex which plays an essential role in the initiation of DNA replication by binding to DNA replication origins and facilitating the assembly of the DNA replication machinery.[12] [UniProtKB:P40359] [MCM7_YEAST] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity.[13] [14] [MCM4_YEAST] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity. Required for S phase execution.[15] [16] [CDC45_YEAST] Required for initiation of chromosomal DNA replication. Acts at the origin of replication. Also has a role in minichromosome maintenance.[17] [18] Publication Abstract from PubMedThe eukaryotic CMG (Cdc45, Mcm2-7, GINS) helicase consists of the Mcm2-7 hexameric ring along with five accessory factors. The Mcm2-7 heterohexamer, like other hexameric helicases, is shaped like a ring with two tiers, an N-tier ring composed of the N-terminal domains, and a C-tier of C-terminal domains; the C-tier contains the motor. In principle, either tier could translocate ahead of the other during movement on DNA. We have used cryo-EM single-particle 3D reconstruction to solve the structure of CMG in complex with a DNA fork. The duplex stem penetrates into the central channel of the N-tier and the unwound leading single-strand DNA traverses the channel through the N-tier into the C-tier motor, 5'-3' through CMG. Therefore, the N-tier ring is pushed ahead by the C-tier ring during CMG translocation, opposite the currently accepted polarity. The polarity of the N-tier ahead of the C-tier places the leading Pol epsilon below CMG and Pol alpha-primase at the top of CMG at the replication fork. Surprisingly, the new N-tier to C-tier polarity of translocation reveals an unforeseen quality-control mechanism at the origin. Thus, upon assembly of head-to-head CMGs that encircle double-stranded DNA at the origin, the two CMGs must pass one another to leave the origin and both must remodel onto opposite strands of single-stranded DNA to do so. We propose that head-to-head motors may generate energy that underlies initial melting at the origin. Structure of eukaryotic CMG helicase at a replication fork and implications to replisome architecture and origin initiation.,Georgescu R, Yuan Z, Bai L, de Luna Almeida Santos R, Sun J, Zhang D, Yurieva O, Li H, O'Donnell ME Proc Natl Acad Sci U S A. 2017 Jan 17. pii: 201620500. doi:, 10.1073/pnas.1620500114. PMID:28096349[19] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Baker's yeast | DNA helicase | Large Structures | Donnell, M E.O | Georgescu, R | Li, B | Li, H | Santos, R | Sun, J | Yuan, Z | Yurieva, O | Zhang, D | Cmg helicase | Dna polymerase | Dna replication | Origin initiation | Replication | Replisome
