The Structural Properties in Solution of the Intrinsically
Mixed Folded Protein Ataxin-3

J 2018

The Structural Properties in Solution of the Intrinsically Mixed Folded Protein Ataxin-3

SICORELLO, A., G. KELLY, A. OREGIONI, Jiří NOVÁČEK, Vladimír SKLENÁŘ et. al.

Základní údaje

Originální název

The Structural Properties in Solution of the Intrinsically Mixed Folded Protein Ataxin-3

Autoři

SICORELLO, A. (826 Velká Británie a Severní Irsko), G. KELLY (826 Velká Británie a Severní Irsko), A. OREGIONI (826 Velká Británie a Severní Irsko), Jiří NOVÁČEK (203 Česká republika, garant, domácí), Vladimír SKLENÁŘ (203 Česká republika, domácí) a A. PASTORE (380 Itálie)

Vydání

Biophysical Journal, Bethesda, USA, Biophysical Society, 2018, 0006-3495

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 3.665

Kód RIV

RIV/00216224:14740/18:00106667

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1016/j.bpj.2018.05.029

UT WoS

000437825800008

Klíčová slova anglicky

EXPANDED POLYGLUTAMINE PROTEIN; LINEAR LATTICE MODEL; EXON-1 N-TERMINUS; JOSEPHIN DOMAIN; SECONDARY STRUCTURE; NMR-SPECTROSCOPY; DISORDERED PROTEINS; UBIQUITIN-BINDING; FOURIER-TRANSFORM; DISEASE PROTEIN

Štítky

CF CRYO, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 19. 3. 2019 16:30, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

It has increasingly become clear over the last two decades that proteins can contain both globular domains and intrinsically unfolded regions that can both contribute to function. Although equally interesting, the disordered regions are difficult to study, because they usually do not crystallize unless bound to partners and are not easily amenable to cryo-electron microscopy studies. NMR spectroscopy remains the best technique to capture the structural features of intrinsically mixed folded proteins and describe their dynamics. These studies rely on the successful assignment of the spectrum, a task not easy per se given the limited spread of the resonances of the disordered residues. Here, we describe the structural properties of ataxin-3, the protein responsible for the neurodegenerative Machado-Joseph disease. Ataxin-3 is a 42-kDa protein containing a globular N-terminal Josephin domain and a C-terminal tail that comprises 13 polyglutamine repeats within a low complexity region. We developed a strategy that allowed us to achieve 87% assignment of the NMR spectrum using a mixed protocol based on high-dimensionality, high-resolution experiments and different labeling schemes. Thanks to the almost complete spectral assignment, we proved that the C-terminal tail is flexible, with extended helical regions, and interacts only marginally with the rest of the protein. We could also, for the first time to our knowledge, observe the structural propensity of the polyglutamine repeats within the context of the full-length protein and show that its structure is stabilized by the preceding region.

Návaznosti

LM2015043, projekt VaV

Název: Česká infrastruktura pro integrativní strukturní biologii (Akronym: CIISB)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Czech Infrastructure for Integrative Structural Biology

Citovat

SICORELLO, A., G. KELLY, A. OREGIONI, Jiří NOVÁČEK, Vladimír SKLENÁŘ a A. PASTORE. The Structural Properties in Solution of the Intrinsically Mixed Folded Protein Ataxin-3. Biophysical Journal. Bethesda, USA: Biophysical Society, 2018, roč. 115, č. 1, s. 59-71. ISSN 0006-3495. Dostupné z: https://dx.doi.org/10.1016/j.bpj.2018.05.029.

@article{1507919,
   author = {Sicorello, A. and Kelly, G. and Oregioni, A. and Nováček, Jiří and Sklenář, Vladimír and Pastore, A.},
   article_location = {Bethesda, USA},
   article_number = {1},
   doi = {http://dx.doi.org/10.1016/j.bpj.2018.05.029},
   keywords = {EXPANDED POLYGLUTAMINE PROTEIN; LINEAR LATTICE MODEL; EXON-1 N-TERMINUS; JOSEPHIN DOMAIN; SECONDARY STRUCTURE; NMR-SPECTROSCOPY; DISORDERED PROTEINS; UBIQUITIN-BINDING; FOURIER-TRANSFORM; DISEASE PROTEIN},
   language = {eng},
   issn = {0006-3495},
   journal = {Biophysical Journal},
   title = {The Structural Properties in Solution of the Intrinsically Mixed Folded Protein Ataxin-3},
   volume = {115},
   year = {2018}
}

TY  - JOUR
ID  - 1507919
AU  - Sicorello, A. - Kelly, G. - Oregioni, A. - Nováček, Jiří - Sklenář, Vladimír - Pastore, A.
PY  - 2018
TI  - The Structural Properties in Solution of the Intrinsically Mixed Folded Protein Ataxin-3
JF  - Biophysical Journal
VL  - 115
IS  - 1
SP  - 59-71
EP  - 59-71
PB  - Biophysical Society
SN  - 00063495
KW  - EXPANDED POLYGLUTAMINE PROTEIN
KW  - LINEAR LATTICE MODEL
KW  - EXON-1 N-TERMINUS
KW  - JOSEPHIN DOMAIN
KW  - SECONDARY STRUCTURE
KW  - NMR-SPECTROSCOPY
KW  - DISORDERED PROTEINS
KW  - UBIQUITIN-BINDING
KW  - FOURIER-TRANSFORM
KW  - DISEASE PROTEIN
N2  - It has increasingly become clear over the last two decades that proteins can contain both globular domains and intrinsically unfolded regions that can both contribute to function. Although equally interesting, the disordered regions are difficult to study, because they usually do not crystallize unless bound to partners and are not easily amenable to cryo-electron microscopy studies. NMR spectroscopy remains the best technique to capture the structural features of intrinsically mixed folded proteins and describe their dynamics. These studies rely on the successful assignment of the spectrum, a task not easy per se given the limited spread of the resonances of the disordered residues. Here, we describe the structural properties of ataxin-3, the protein responsible for the neurodegenerative Machado-Joseph disease. Ataxin-3 is a 42-kDa protein containing a globular N-terminal Josephin domain and a C-terminal tail that comprises 13 polyglutamine repeats within a low complexity region. We developed a strategy that allowed us to achieve 87% assignment of the NMR spectrum using a mixed protocol based on high-dimensionality, high-resolution experiments and different labeling schemes. Thanks to the almost complete spectral assignment, we proved that the C-terminal tail is flexible, with extended helical regions, and interacts only marginally with the rest of the protein. We could also, for the first time to our knowledge, observe the structural propensity of the polyglutamine repeats within the context of the full-length protein and show that its structure is stabilized by the preceding region.
ER  -

SICORELLO, A., G. KELLY, A. OREGIONI, Jiří NOVÁČEK, Vladimír SKLENÁŘ a A. PASTORE. The Structural Properties in Solution of the Intrinsically Mixed Folded Protein Ataxin-3. \textit{Biophysical Journal}. Bethesda, USA: Biophysical Society, 2018, roč.~115, č.~1, s.~59-71. ISSN~0006-3495. Dostupné z: https://dx.doi.org/10.1016/j.bpj.2018.05.029.

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