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-Structure paper
Title | Structural study of the N-terminal domain of human MCM8/9 complex. |
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Journal, issue, pages | Structure, Vol. 29, Issue 10, Page 1171-11181.e4, Year 2021 |
Publish date | Oct 7, 2021 |
Authors | Jun Li / Daqi Yu / Lan Liu / Huanhuan Liang / Qi Ouyang / Yingfang Liu / |
PubMed Abstract | MCM8/9 is a complex involved in homologous recombination (HR) repair pathway. MCM8/9 dysfunction can cause genome instability and result in primary ovarian insufficiency (POI). However, the mechanism ...MCM8/9 is a complex involved in homologous recombination (HR) repair pathway. MCM8/9 dysfunction can cause genome instability and result in primary ovarian insufficiency (POI). However, the mechanism underlying these effects is largely unknown. Here, we report crystal structures of the N-terminal domains (NTDs) of MCM8 and MCM9, and build a ring-shaped NTD structure based on a 6.6 Å resolution cryoelectron microscopy map. This shows that the MCM8/9 complex forms a 3:3 heterohexamer in an alternating pattern. A positively charged DNA binding channel and a putative ssDNA exit pathway for fork DNA unwinding are revealed. Based on the atomic model, the potential effects of the clinical POI mutants are interpreted. Surprisingly, the zinc-finger motifs are found to be capable of binding an iron atom as well. Overall, our results provide a model for the formation of the MCM8/9 complex and provide a path for further studies. |
External links | Structure / PubMed:34043945 |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 2.55 - 7.1 Å |
Structure data | EMDB-0823: EMDB-0824: PDB-7dp3: PDB-7dpd: |
Chemicals | ChemComp-ZN: ChemComp-HOH: ChemComp-NA: |
Source |
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Keywords | DNA BINDING PROTEIN / Zinc Finger / DNA binding |