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

EID Scopus

2-s2.0-85085187710

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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