Multiple Recognition Motifs in Nucleoporin Nup159 Provide a
Stable and Rigid Nup159-Dyn2 Assembly

J 2013

Multiple Recognition Motifs in Nucleoporin Nup159 Provide a Stable and Rigid Nup159-Dyn2 Assembly

NYARKO, Afua, Yujuan SONG, Jiří NOVÁČEK, Lukáš ŽÍDEK, Elisar BARBAR et. al.

Základní údaje

Originální název

Multiple Recognition Motifs in Nucleoporin Nup159 Provide a Stable and Rigid Nup159-Dyn2 Assembly

Autoři

NYARKO, Afua (840 Spojené státy), Yujuan SONG (840 Spojené státy), Jiří NOVÁČEK (203 Česká republika, domácí), Lukáš ŽÍDEK (203 Česká republika, garant, domácí) a Elisar BARBAR (840 Spojené státy)

Vydání

Journal of Biological Chemistry, Bethesda, USA, Amer. Soc. Biochem. Mol. Biol. 2013, 0021-9258

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10610 Biophysics

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.600

Kód RIV

RIV/00216224:14740/13:00066050

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1074/jbc.M112.432831

UT WoS

000314211500046

Klíčová slova anglicky

Intrinsic disorder NMR ITC polybivalency enthalpy/entropy balance

Štítky

ok, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 26. 9. 2013 11:05, Olga Křížová

Anotace

V originále

Dyn2 is the yeast ortholog of the molecular hub LC8, which binds disordered proteins and promotes their self-association and higher order assembly. Dyn2 is proposed to dimerize and stabilize the Nup82-Nsp1-Nup159 complex of the nuclear pore assembly through its interaction with nucleoporin Nup159. Nup159 has six LC8 recognition motifs separated by short linkers. NMR experiments reported here show that the Dyn2 binding domain of Nup159 is intrinsically disordered and that binding of one equivalent of Dyn2 dimer aligns two Nup159 chains along the full Dyn2 binding domain to form a bivalent scaffold that promotes binding of other Dyn2 dimers. Isothermal titration calorimetry of Dyn2 binding to Nup constructs of increasing lengths determine that the third LC8 recognition motifs does not bind Dyn2. A new approach to identifying active LC8 recognition motifs based on NMR-detected beta-sheet propensities is presented. Isothermal titration calorimetry experiments also show that, due to unfavorable entropy changes, a Nup-Dyn2 complex with three Dyn2 dimers is more stable than the wildtype complex with five Dyn2 dimers. The calorimetric results argue that, from a thermodynamics perspective, only three Dyn2 dimers are needed for optimal stability and suggest that the evolutionary adaptation of multiple tandem LC8 recognition motifs imparts to the complex other properties such as rigidity and a kink in the rod-like structure. These findings extend the repertoire of functions of intrinsically disordered protein to fine-tuning and versatile assembly of higher order macromolecular complexes.

Návaznosti

GAP206/11/0758, projekt VaV

Název: Vývoj metodologie s vysokým rozlišením pro NMR studie neuspořádaných proteinů s vysoce degenerovanými rezonančními frekvencemi (Akronym: HIGHRES)

Investor: Grantová agentura ČR, Vývoj metodologie s vysokým rozlišením pro NMR studie neuspořádaných proteinů s vysoce degenerovanými rezonančními frekvencemi

Citovat

NYARKO, Afua, Yujuan SONG, Jiří NOVÁČEK, Lukáš ŽÍDEK a Elisar BARBAR. Multiple Recognition Motifs in Nucleoporin Nup159 Provide a Stable and Rigid Nup159-Dyn2 Assembly. Journal of Biological Chemistry. Bethesda, USA: Amer. Soc. Biochem. Mol. Biol., 2013, roč. 288, č. 4, s. 2614-2622. ISSN 0021-9258. Dostupné z: https://dx.doi.org/10.1074/jbc.M112.432831.

@article{1091436,
   author = {Nyarko, Afua and Song, Yujuan and Nováček, Jiří and Žídek, Lukáš and Barbar, Elisar},
   article_location = {Bethesda, USA},
   article_number = {4},
   doi = {http://dx.doi.org/10.1074/jbc.M112.432831},
   keywords = {Intrinsic disorder NMR ITC polybivalency enthalpy/entropy balance},
   language = {eng},
   issn = {0021-9258},
   journal = {Journal of Biological Chemistry},
   title = {Multiple Recognition Motifs in Nucleoporin Nup159 Provide a Stable and Rigid Nup159-Dyn2 Assembly},
   url = {http://www.jbc.org/content/288/4/2614},
   volume = {288},
   year = {2013}
}

TY  - JOUR
ID  - 1091436
AU  - Nyarko, Afua - Song, Yujuan - Nováček, Jiří - Žídek, Lukáš - Barbar, Elisar
PY  - 2013
TI  - Multiple Recognition Motifs in Nucleoporin Nup159 Provide a Stable and Rigid Nup159-Dyn2 Assembly
JF  - Journal of Biological Chemistry
VL  - 288
IS  - 4
SP  - 2614-2622
EP  - 2614-2622
PB  - Amer. Soc. Biochem. Mol. Biol.
SN  - 00219258
KW  - Intrinsic disorder NMR ITC polybivalency enthalpy/entropy balance
UR  - http://www.jbc.org/content/288/4/2614
L2  - http://www.jbc.org/content/288/4/2614
N2  - Dyn2 is the yeast ortholog of the molecular hub LC8, which binds disordered proteins and promotes their self-association and higher order assembly. Dyn2 is proposed to dimerize and stabilize the Nup82-Nsp1-Nup159 complex of the nuclear pore assembly through its interaction with nucleoporin Nup159. Nup159 has six LC8 recognition motifs separated by short linkers. NMR experiments reported here show that the Dyn2 binding domain of Nup159 is intrinsically disordered and that binding of one equivalent of Dyn2 dimer aligns two Nup159 chains along the full Dyn2 binding domain to form a bivalent scaffold that promotes binding of other Dyn2 dimers. Isothermal titration calorimetry of Dyn2 binding to Nup constructs of increasing lengths determine that the third LC8 recognition motifs does not bind Dyn2. A new approach to identifying active LC8 recognition motifs based on NMR-detected beta-sheet propensities is presented. Isothermal titration calorimetry experiments also show that, due to unfavorable entropy changes, a Nup-Dyn2 complex with three Dyn2 dimers is more stable than the wildtype complex with five Dyn2 dimers. The calorimetric results argue that, from a thermodynamics perspective, only three Dyn2 dimers are needed for optimal stability and suggest that the evolutionary adaptation of multiple tandem LC8 recognition motifs imparts to the complex other properties such as rigidity and a kink in the rod-like structure. These findings extend the repertoire of functions of intrinsically disordered protein to fine-tuning and versatile assembly of higher order macromolecular complexes.
ER  -

NYARKO, Afua, Yujuan SONG, Jiří NOVÁČEK, Lukáš ŽÍDEK a Elisar BARBAR. Multiple Recognition Motifs in Nucleoporin Nup159 Provide a Stable and Rigid Nup159-Dyn2 Assembly. \textit{Journal of Biological Chemistry}. Bethesda, USA: Amer. Soc. Biochem. Mol. Biol., 2013, roč.~288, č.~4, s.~2614-2622. ISSN~0021-9258. Dostupné z: https://dx.doi.org/10.1074/jbc.M112.432831.

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