Molecular insights into the architecture of the human SMC5/6
complex

J 2020

Molecular insights into the architecture of the human SMC5/6 complex

ADAMUS, Marek, Edit LELKES, David POTĚŠIL, Sri Ranjani GANJI, Peter KOLESÁR et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

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

Abstract

V originále

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 project

Name: Úloha Nse1/Nse3/Nse4, E3-ubikvitin ligásy, ve stabilitě genomu

Investor: Czech Science Foundation

LM2018140, research and development project

Name: e-Infrastruktura CZ (Acronym: e-INFRA CZ)

Investor: Ministry of Education, Youth and Sports of the CR

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

90127, large research infrastructures

Name: CIISB II

Citovat

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, 2020, vol. 432, No 13, p. 3820-3837. ISSN 0022-2836. Available from: https://dx.doi.org/10.1016/j.jmb.2020.04.024.

@article{1662630,
   author = {Adamus, Marek and Lelkes, Edit and Potěšil, David and Ganji, Sri Ranjani and Kolesár, Peter and Zábrady, Kateřina and Zdráhal, Zbyněk and Paleček, Jan},
   article_location = {London},
   article_number = {13},
   doi = {http://dx.doi.org/10.1016/j.jmb.2020.04.024},
   keywords = {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},
   language = {eng},
   issn = {0022-2836},
   journal = {Journal of Molecular Biology},
   title = {Molecular insights into the architecture of the human SMC5/6 complex},
   url = {https://doi.org/10.1016/j.jmb.2020.04.024},
   volume = {432},
   year = {2020}
}

TY  - JOUR
ID  - 1662630
AU  - Adamus, Marek - Lelkes, Edit - Potěšil, David - Ganji, Sri Ranjani - Kolesár, Peter - Zábrady, Kateřina - Zdráhal, Zbyněk - Paleček, Jan
PY  - 2020
TI  - Molecular insights into the architecture of the human SMC5/6 complex
JF  - Journal of Molecular Biology
VL  - 432
IS  - 13
SP  - 3820-3837
EP  - 3820-3837
PB  - Academic Press ltd-Elsevier Science ltd
SN  - 00222836
KW  - human SMC5/6 complex architecture
KW  - SMC5-SMC6 dimer coiled-coil arms
KW  - NSE1-NSE3-NSE4 trimer
KW  - NSE5-NSE6 dimer
KW  - CANIN protein-protein interaction domain
KW  - MAGE domain
UR  - https://doi.org/10.1016/j.jmb.2020.04.024
L2  - https://doi.org/10.1016/j.jmb.2020.04.024
N2  - 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.
ER  -

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. \textit{Journal of Molecular Biology}. London: Academic Press ltd-Elsevier Science ltd, 2020, vol.~432, No~13, p.~3820-3837. ISSN~0022-2836. Available from: https://dx.doi.org/10.1016/j.jmb.2020.04.024.

Detailed Information on Publication Record