Molecular Insights into the Architecture of the Human SMC5/6 Complex
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
32389690
DOI
10.1016/j.jmb.2020.04.024
PII: S0022-2836(20)30322-3
Knihovny.cz E-resources
- Keywords
- CANIN protein–protein interaction domain, MAGE domain, NSE1–NSE3–NSE4 trimer, NSE5–NSE6 dimer, SMC5–SMC6 dimer coiled-coil arms, human SMC5/6 complex architecture,
- MeSH
- Chromosomal Proteins, Non-Histone genetics MeSH
- Humans MeSH
- Protein Multimerization genetics MeSH
- Multiprotein Complexes genetics MeSH
- Mutation MeSH
- DNA Repair genetics MeSH
- Protein Domains genetics MeSH
- Cell Cycle Proteins genetics MeSH
- Carrier Proteins genetics MeSH
- Protein Binding genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Chromosomal Proteins, Non-Histone MeSH
- Multiprotein Complexes MeSH
- NSE4 protein, human MeSH Browser
- NSMCE1 protein, human MeSH Browser
- Cell Cycle Proteins MeSH
- SMC5 protein, human MeSH Browser
- SMC6 protein, human MeSH Browser
- Carrier Proteins MeSH
A family of Structural Maintenance of Chromosome (SMC) complexes is essential for key cellular processes ensuring proper cohesion, condensation and replication. They share a common SMC-kleisin architecture allowing them to embrace DNA. In SMC5/6, the NSE1 and NSE3 KITE and NSE4 kleisin subunits form a stable subcomplex that binds DNA and regulates essential processes. In addition, NSE5 and NSE6 subunits associate with the core SMC5/6 complex and recruit it to DNA repair sites. The architecture of the SMC5/6 complex is crucial for its proper functioning, and mutations within the human SMC5/6 subunits result in severe syndromes. Therefore, we aimed to analyze interactions within the human SMC5/6 complex and determine its detailed architecture. Firstly, we analyzed different parts of SMC5/6 by crosslinking and MS/MS analysis. Our data suggested domain arrangements of hNSE1-hNSE3 and orientation of hNSE4 within the hNSE1-hNSE3-hNSE4 subcomplex. The crosslinking and electron microscopic analysis of the SMC5/6 core complex showed its rod-like architecture with juxtaposed hSMC5-hSMC6 arms. Additionally, we observed fully or partially opened hSMC5-hSMC6 shapes with the hNSE1-hNSE3-hNSE4 trimer localized in the SMC head domains. To complete mapping of the human SMC5/6 complex architecture, we analyzed positions of hNSE5-hNSE6 at the hSMC5-hSMC6 arms. We showed that hNSE6 binding to hNSE5 and the coiled-coil arm of hSMC6 is mediated by a conserved FAM178 domain, which we therefore renamed CANIN (Coiled-coil SMC6 And NSE5 INteracting) domain. Interestingly, hNSE6 bound both hSMC5 and hSMC6 arms, suggesting that hNSE6 may lock the arms and regulate the dynamics of the human SMC5/6 complex.
References provided by Crossref.org
The SAGA histone acetyltransferase module targets SMC5/6 to specific genes
Role of Nse1 Subunit of SMC5/6 Complex as a Ubiquitin Ligase
