2O8F: Human Mutsalpha (Msh2MSH6) BOUND TO DNA WITH A SINGLE BASE T INSERT

Citation:
Abstract
Mismatch repair (MMR) ensures the fidelity of DNA replication, initiates the cellular response to certain classes of DNA damage, and has been implicated in the generation of immune diversity. Each of these functions depends on MutSalpha (MSH2*MSH6 heterodimer). Inactivation of this protein complex is responsible for tumor development in about half of known hereditary nonpolyposis colorectal cancer kindreds and also occurs in sporadic tumors in a variety of tissues. Here, we describe a series of crystal structures of human MutSalpha bound to different DNA substrates, each known to elicit one of the diverse biological responses of the MMR pathway. All lesions are recognized in a similar manner, indicating that diversity of MutSalpha-dependent responses to DNA lesions is generated in events downstream of this lesion recognition step. This study also allows rigorous mapping of cancer-causing mutations and furthermore suggests structural pathways for allosteric communication between different regions within the heterodimer.
PDB ID: 2O8FDownload
MMDB ID: 53939
PDB Deposition Date: 2006/12/12
Updated in MMDB: 2007/10
Experimental Method:
x-ray diffraction
Resolution: 3.25  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 2O8F: tetrameric; determined by author
Molecular Components in 2O8F
Label Count Molecule
Proteins (2 molecules)
1
DNA Mismatch Repair Protein Msh2(Gene symbol: MSH2)
Molecule annotation
1
DNA Mismatch Repair Protein Msh6(Gene symbol: MSH6)
Molecule annotation
Nucleotides(2 molecules)
1
5'-d(*gp*ap*cp*gp*gp*cp*cp*gp*cp*cp*gp*cp*tp*ap*gp*cp*g)- 3'
Molecule annotation
1
5'-d(*cp*gp*cp*tp*ap*gp*cp*gp*tp*gp*cp*gp*gp*cp*cp*gp*tp*c) -3'
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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