ADAMUS, Marek, Edit LELKES, David POTĚŠIL, Sri Ranjani GANJI, Peter KOLESÁR, Kateřina ZÁBRADY, Zbyněk ZDRÁHAL and Jan PALEČEK. Molecular insights into the architecture of the human SMC5/6 complex. Journal of Molecular Biology. London: Academic Press ltd-Elsevier Science ltd, vol. 432, No 13, p. 3820-3837. ISSN 0022-2836. doi:10.1016/j.jmb.2020.04.024. 2020.
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Basic information
Original name Molecular insights into the architecture of the human SMC5/6 complex
Name in Czech Molekulární vhled do architektury lidského komplexu SMC5/6
Authors ADAMUS, Marek (203 Czech Republic, belonging to the institution), Edit LELKES (703 Slovakia, belonging to the institution), David POTĚŠIL (203 Czech Republic, belonging to the institution), Sri Ranjani GANJI (356 India, belonging to the institution), Peter KOLESÁR (703 Slovakia, belonging to the institution), Kateřina ZÁBRADY (203 Czech Republic, belonging to the institution), Zbyněk ZDRÁHAL (203 Czech Republic, belonging to the institution) and Jan PALEČEK (203 Czech Republic, guarantor, belonging to the institution).
Edition Journal of Molecular Biology, London, Academic Press ltd-Elsevier Science ltd, 2020, 0022-2836.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10608 Biochemistry and molecular biology
Country of publisher United Kingdom of Great Britain and Northern Ireland
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 5.469
RIV identification code RIV/00216224:14310/20:00114182
Organization unit Faculty of Science
Doi http://dx.doi.org/10.1016/j.jmb.2020.04.024
UT WoS 000541931500007
Keywords in English human SMC5/6 complex architecture; SMC5-SMC6 dimer coiled-coil arms; NSE1-NSE3-NSE4 trimer; NSE5-NSE6 dimer; CANIN protein-protein interaction domain; MAGE domain
Tags CF CRYO, CF PROT, rivok
Tags International impact, Reviewed
Changed by Changed by: Mgr. Marie Šípková, DiS., učo 437722. Changed: 19/10/2020 16:54.
Abstract
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.
Links
GA18-02067S, research and development projectName: Úloha Nse1/Nse3/Nse4, E3-ubikvitin ligásy, ve stabilitě genomu
Investor: Czech Science Foundation
LM2018127, research and development projectName: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)
Investor: Ministry of Education, Youth and Sports of the CR
LM2018140, research and development projectName: e-Infrastruktura CZ (Acronym: e-INFRA CZ)
Investor: Ministry of Education, Youth and Sports of the CR
LQ1601, research and development projectName: CEITEC 2020 (Acronym: CEITEC2020)
Investor: Ministry of Education, Youth and Sports of the CR
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