3T1I: Crystal Structure Of Human Mre11: Understanding Tumorigenic Mutations

Mre11 plays an important role in repairing damaged DNA by cleaving broken ends and by providing a platform for other DNA repair proteins. Various Mre11 mutations have been identified in several types of cancer. We have determined the crystal structure of the human Mre11 core (hMre11), which contains the nuclease and capping domains. hMre11 dimerizes through the interfaces between loop beta3-alpha3 from one Mre11 and loop beta4-beta5 from another Mre11, and between loop alpha2-beta3 from one Mre11 and helices alpha2 and alpha3 from another Mre11, and assembles into a completely different dimeric architecture compared with bacterial or archaeal Mre11 homologs. Nbs1 binds to the region containing loop alpha2-beta3 which participates in dimerization. The hMre11 structure in conjunction with biochemical analyses reveals that many tumorigenic mutations are primarily associated with Nbs1 binding and partly with nuclease activities, providing a framework for understanding how mutations inactivate Mre11.
PDB ID: 3T1IDownload
MMDB ID: 95380
PDB Deposition Date: 2011/7/22
Updated in MMDB: 2011/12
Experimental Method:
x-ray diffraction
Resolution: 3  Å
Source Organism:
Similar Structures:
Biological Unit for 3T1I: dimeric; determined by author and by software (PISA)
Molecular Components in 3T1I
Label Count Molecule
Proteins (2 molecules)
Double-strand Break Repair Protein Mre11a(Gene symbol: MRE11)
Molecule annotation
Chemicals (12 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB