4YWL

Pyrococcus furiosus MCM N-terminal domain F179A point mutant pentameric ring

Summary for 4YWL

• Entry DOI: 10.2210/pdb4ywl/pdb
• Related: 4POF 4YWK 4YWM
• Descriptor: Cell division control protein 21, ZINC ION, SULFATE ION (3 entities in total)
• Functional Keywords: mcm, helicase, replication, ob-fold, cell cycle
• Biological source: Pyrococcus furiosus
• Total number of polymer chains: 10
• Total formula weight: 294764.83

Authors

Froelich, C.A.,Enemark, E.J. (deposition date: 2015-03-20, release date: 2015-09-23, Last modification date: 2023-09-27)

Primary citation

Froelich, C.A.,Nourse, A.,Enemark, E.J.
MCM ring hexamerization is a prerequisite for DNA-binding.
Nucleic Acids Res., 43:9553-9563, 2015

PubMed Abstract: The hexameric Minichromosome Maintenance (MCM) protein complex forms a ring that unwinds DNA at the replication fork in eukaryotes and archaea. Our recent crystal structure of an archaeal MCM N-terminal domain bound to single-stranded DNA (ssDNA) revealed ssDNA associating across tight subunit interfaces but not at the loose interfaces, indicating that DNA-binding is governed not only by the DNA-binding residues of the subunits (MCM ssDNA-binding motif, MSSB) but also by the relative orientation of the subunits. We now extend these findings by showing that DNA-binding by the MCM N-terminal domain of the archaeal organism Pyrococcus furiosus occurs specifically in the hexameric oligomeric form. We show that mutants defective for hexamerization are defective in binding ssDNA despite retaining all the residues observed to interact with ssDNA in the crystal structure. One mutation that exhibits severely defective hexamerization and ssDNA-binding is at a conserved phenylalanine that aligns with the mouse Mcm4(Chaos3) mutation associated with chromosomal instability, cancer, and decreased intersubunit association.

PubMed: 26365238
DOI: 10.1093/nar/gkv914

Experimental method

X-RAY DIFFRACTION (3.2 Å)