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.

Základní údaje

Originální název

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

Název česky

Molekulární vhled do architektury lidského komplexu SMC5/6

Autoři

ADAMUS, Marek (203 Česká republika, domácí), Edit LELKES (703 Slovensko, domácí), David POTĚŠIL (203 Česká republika, domácí), Sri Ranjani GANJI (356 Indie, domácí), Peter KOLESÁR (703 Slovensko, domácí), Kateřina ZÁBRADY (203 Česká republika, domácí), Zbyněk ZDRÁHAL (203 Česká republika, domácí) a Jan PALEČEK (203 Česká republika, garant, domácí)

Vydání

Journal of Molecular Biology, London, Academic Press ltd-Elsevier Science ltd, 2020, 0022-2836

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 5.469

Kód RIV

RIV/00216224:14310/20:00114182

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1016/j.jmb.2020.04.024

UT WoS

000541931500007

Klíčová slova anglicky

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

Štítky

CF CRYO, CF PROT, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 27. 10. 2024 14:09, Ing. Martina Blahová

Anotace

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.

Návaznosti

GA18-02067S, projekt VaV

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

Investor: Grantová agentura ČR, Úloha Nse1/Nse3/Nse4, E3-ubikvitin ligásy, ve stabilitě genomu

LM2018140, projekt VaV

Název: e-Infrastruktura CZ (Akronym: e-INFRA CZ)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, e-Infrastruktura CZ

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

90127, velká výzkumná infrastruktura

Název: CIISB II

Citovat

ADAMUS, Marek, Edit LELKES, David POTĚŠIL, Sri Ranjani GANJI, Peter KOLESÁR, Kateřina ZÁBRADY, Zbyněk ZDRÁHAL a 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, roč. 432, č. 13, s. 3820-3837. ISSN 0022-2836. Dostupné z: 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 a 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, roč.~432, č.~13, s.~3820-3837. ISSN~0022-2836. Dostupné z: https://dx.doi.org/10.1016/j.jmb.2020.04.024.

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