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The GCM domain is a Zn-coordinating DNA-binding domain
Serge X Cohen1, Martine Moulin, Oliver Schilling
1European Molecular Biology Laboratory, Grenoble Outstation, B.P. 181, France.
FEBS Letters
|September 26, 2002
Summary
Glial cells missing (GCM) proteins regulate development. This study reveals the GCM domain binds DNA via a novel zinc-coordinating structure, crucial for its function.
Area of Science:
- Molecular Biology
- Developmental Biology
- Structural Biology
Background:
- Glial cells missing (GCM) proteins are transcriptional regulators.
- They possess a conserved DNA-binding domain essential for developmental processes.
- The precise structural mechanism of GCM DNA binding was previously unclear.
Purpose of the Study:
- To elucidate the structural basis of the GCM domain's DNA-binding capability.
- To characterize the role of metal ions in GCM domain structure and function.
Main Methods:
- Bacterial expression of the mouse GCM homolog a (GCMa) domain.
- Extended X-ray absorption fine structure (EXAFS) analysis.
- Particle-induced X-ray emission (PIXE) analysis.
- Treatment with the zinc chelator phenanthroline.
Main Results:
- The GCM domain contains two zinc (Zn) atoms coordinated by cysteine and histidine residues.
- Zn ions are located internally within the GCM domain structure.
- Removal of Zn ions under denaturing conditions disrupts the GCM domain structure and abolishes DNA binding.
Conclusions:
- The GCM domain represents a novel class of zinc-coordinating DNA-binding domains.
- Zinc coordination is critical for maintaining the structural integrity and DNA-binding function of the GCM domain.
- This finding provides new insights into the molecular mechanisms of transcriptional regulation by GCM proteins.