EMD-1834
Planar configuration of the Drosophila melanogaster Mcm2-7 complex
EMD-1834
Single-particle33.0 Å
Deposition: 28/11/2010Map released: 08/04/2011
Last modified: 15/04/2011
Sample Organism:
Drosophila melanogaster
Sample: Mcm2-7
Deposition Authors: Costa A, Ilves I
,
Tamberg N,
Petojevic T,
Nogales E,
Botchan M,
Berger JM
Sample: Mcm2-7
Deposition Authors: Costa A, Ilves I
,
Tamberg N,
Petojevic T,
Nogales E,
Botchan M,
Berger JM
The structural basis for MCM2-7 helicase activation by GINS and Cdc45.
Costa A,
Ilves I ,
Tamberg N,
Petojevic T,
Nogales E,
Botchan MR,
Berger JM
(2011) Nat. Struct. Mol. Biol. , 18 , 471 - 477
,
Tamberg N,
Petojevic T,
Nogales E,
Botchan MR,
Berger JM
(2011) Nat. Struct. Mol. Biol. , 18 , 471 - 477
Abstract:
Two central steps for initiating eukaryotic DNA replication involve loading of the Mcm2-7 helicase onto double-stranded DNA and its activation by GINS-Cdc45. To better understand these events, we determined the structures of Mcm2-7 and the CMG complex by using single-particle electron microscopy. Mcm2-7 adopts two conformations--a lock-washer-shaped spiral state and a planar, gapped-ring form--in which Mcm2 and Mcm5 flank a breach in the helicase perimeter. GINS and Cdc45 bridge this gap, forming a topologically closed assembly with a large interior channel; nucleotide binding further seals off the discontinuity between Mcm2 and Mcm5, partitioning the channel into two smaller pores. Together, our data help explain how GINS and Cdc45 activate Mcm2-7, indicate that Mcm2-7 loading may be assisted by a natural predisposition of the hexamer to form open rings, and suggest a mechanism by which the CMG complex assists DNA strand separation.
Two central steps for initiating eukaryotic DNA replication involve loading of the Mcm2-7 helicase onto double-stranded DNA and its activation by GINS-Cdc45. To better understand these events, we determined the structures of Mcm2-7 and the CMG complex by using single-particle electron microscopy. Mcm2-7 adopts two conformations--a lock-washer-shaped spiral state and a planar, gapped-ring form--in which Mcm2 and Mcm5 flank a breach in the helicase perimeter. GINS and Cdc45 bridge this gap, forming a topologically closed assembly with a large interior channel; nucleotide binding further seals off the discontinuity between Mcm2 and Mcm5, partitioning the channel into two smaller pores. Together, our data help explain how GINS and Cdc45 activate Mcm2-7, indicate that Mcm2-7 loading may be assisted by a natural predisposition of the hexamer to form open rings, and suggest a mechanism by which the CMG complex assists DNA strand separation.