Addressing the Molecular Mechanism of Longitudinal Lamin Assembly Using Chimeric Fusions

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F20%3A00533355" target="_blank" >RIV/61388971:_____/20:00533355 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11310/20:10413327

Výsledek na webu

<a href="https://www.mdpi.com/2073-4409/9/7/1633" target="_blank" >https://www.mdpi.com/2073-4409/9/7/1633</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cells9071633" target="_blank" >10.3390/cells9071633</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Addressing the Molecular Mechanism of Longitudinal Lamin Assembly Using Chimeric Fusions

Popis výsledku v původním jazyce

The molecular architecture and assembly mechanism of intermediate filaments have been enigmatic for decades. Among those, lamin filaments are of particular interest due to their universal role in cell nucleus and numerous disease-related mutations. Filament assembly is driven by specific interactions of the elementary dimers, which consist of the central coiled-coil rod domain flanked by non-helical head and tail domains. We aimed to investigate the longitudinal 'head-to-tail' interaction of lamin dimers (the so-called A(CN)interaction), which is crucial for filament assembly. To this end, we prepared a series of recombinant fragments of human lamin A centred around the N- and C-termini of the rod. The fragments were stabilized by fusions to heterologous capping motifs which provide for a correct formation of parallel, in-register coiled-coil dimers. As a result, we established crystal structures of two N-terminal fragments one of which highlights the propensity of the coiled-coil to open up, and one C-terminal rod fragment. Additional studies highlighted the capacity of such N- and C-terminal fragments to form specific complexes in solution, which were further characterized using chemical cross-linking. These data yielded a molecular model of the A(CN)complex which features a 6.5 nm overlap of the rod ends.

Název v anglickém jazyce

Addressing the Molecular Mechanism of Longitudinal Lamin Assembly Using Chimeric Fusions

Popis výsledku anglicky

The molecular architecture and assembly mechanism of intermediate filaments have been enigmatic for decades. Among those, lamin filaments are of particular interest due to their universal role in cell nucleus and numerous disease-related mutations. Filament assembly is driven by specific interactions of the elementary dimers, which consist of the central coiled-coil rod domain flanked by non-helical head and tail domains. We aimed to investigate the longitudinal 'head-to-tail' interaction of lamin dimers (the so-called A(CN)interaction), which is crucial for filament assembly. To this end, we prepared a series of recombinant fragments of human lamin A centred around the N- and C-termini of the rod. The fragments were stabilized by fusions to heterologous capping motifs which provide for a correct formation of parallel, in-register coiled-coil dimers. As a result, we established crystal structures of two N-terminal fragments one of which highlights the propensity of the coiled-coil to open up, and one C-terminal rod fragment. Additional studies highlighted the capacity of such N- and C-terminal fragments to form specific complexes in solution, which were further characterized using chemical cross-linking. These data yielded a molecular model of the A(CN)complex which features a 6.5 nm overlap of the rod ends.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10606 - Microbiology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cells

ISSN

2073-4409

e-ISSN

—

Svazek periodika

9

Číslo periodika v rámci svazku

7

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

20

Strana od-do

1633

Kód UT WoS článku

000554089600001

EID výsledku v databázi Scopus

2-s2.0-85087814133