Structure Basis for Shaping the Nse4 Protein by the Nse1 and Nse3 Dimer within the Smc5/6 Complex
| Autor: | Xiaolan Zhao, Shibai Li, Jin Woo Shin, Aera Jo, Yunje Cho |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Lung Diseases
Models Molecular Protein Folding Chromosomal Proteins Non-Histone Protein Conformation Chromosome replication Dimer Dna interaction Xenopus Xenopus Proteins Closed conformation Crystallography X-Ray Article 03 medical and health sciences chemistry.chemical_compound Xenopus laevis 0302 clinical medicine Structural Biology Animals Amino Acid Sequence Molecular Biology 030304 developmental biology 0303 health sciences biology Immunologic Deficiency Syndromes Chromosome Breakage DNA biology.organism_classification DNA-Binding Proteins chemistry Prokaryotic Cells Lung disease Multiprotein Complexes Mutation Biophysics Chromosome breakage Protein Multimerization 030217 neurology & neurosurgery |
| Zdroj: | J Mol Biol |
| ISSN: | 1089-8638 |
| Popis: | The Smc5/6 complex facilitates chromosome replication and DNA break repair. Within this complex, a subcomplex composed of Nse1, Nse3 and Nse4 is thought to play multiple roles through DNA binding and regulating ATP-dependent activities of the complex. However, how the Nse1-Nse3-Nse4 subcomplex carries out these multiple functions remain unclear. To address this question, we determine the crystal structure of the Xenopus laevis Nse1-Nse3-Nse4 subcomplex at 1.7 A resolution and examine how it interacts with DNA. Our structural analyses show that the Nse1-Nse3 dimer adopts a closed conformation and forms three interfaces with a segment of Nse4, forcing it into a Z-shaped conformation. The Nse1-Nse3-Nse4 structure provides an explanation for how the lung disease immunodeficiency and chromosome breakage syndrome-causing mutations could dislodge Nse4 from Nse1-Nse3. Our DNA binding and mutational analyses reveal that the N-terminal and the middle region of Nse4 contribute to DNA interaction and cell viability. Integrating our data with previous crosslink mass spectrometry data, we propose potential roles of the Nse1-Nse3-Nse4 complex in binding DNA within the Smc5/6 complex. |
| Databáze: | OpenAIRE |
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