Informace o publikaci

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

Název česky Molekulární vhled do architektury lidského komplexu SMC5/6
Autoři

ADAMUS Marek LELKES Edit POTĚŠIL David GANJI Sri Ranjani KOLESÁR Peter ZÁBRADY Kateřina ZDRÁHAL Zbyněk PALEČEK Jan

Rok publikování 2020
Druh Článek v odborném periodiku
Časopis / Zdroj Journal of Molecular Biology
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www https://doi.org/10.1016/j.jmb.2020.04.024
Doi http://dx.doi.org/10.1016/j.jmb.2020.04.024
Klíčová slova 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
Popis 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.
Související projekty: