The molecular architecture of the eukaryotic chaperonin TRiC/CCT

Alexander Leitner, Lukasz A. Joachimiak, Andreas Bracher, Leonie Mönkemeyer, Thomas Walzthoeni, Bryan Chen, Sebastian Pechmann, Susan Holmes, Yao Cong, Boxue Ma, Steve Ludtke, Wah Chiu, F. Ulrich Hartl, Ruedi Aebersold, Judith Frydman

Research output: Contribution to journalArticle

161 Citations (Scopus)

Abstract

TRiC/CCT is a highly conserved and essential chaperonin that uses ATP cycling to facilitate folding of approximately 10% of the eukaryotic proteome. This 1 MDa hetero-oligomeric complex consists of two stacked rings of eight paralogous subunits each. Previously proposed TRiC models differ substantially in their subunit arrangements and ring register. Here, we integrate chemical crosslinking, mass spectrometry, and combinatorial modeling to reveal the definitive subunit arrangement of TRiC. In vivo disulfide mapping provided additional validation for the crosslinking-derived arrangement as the definitive TRiC topology. This subunit arrangement allowed the refinement of a structural model using existing X-ray diffraction data. The structure described here explains all available crosslink experiments, provides a rationale for previously unexplained structural features, and reveals a surprising asymmetry of charges within the chaperonin folding chamber.

Original languageEnglish (US)
Pages (from-to)814-825
Number of pages12
JournalStructure
Volume20
Issue number5
DOIs
StatePublished - May 9 2012
Externally publishedYes

Fingerprint

Chaperonin Containing TCP-1
Chaperonins
Structural Models
Proteome
X-Ray Diffraction
Disulfides
Mass Spectrometry
Adenosine Triphosphate

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Leitner, A., Joachimiak, L. A., Bracher, A., Mönkemeyer, L., Walzthoeni, T., Chen, B., ... Frydman, J. (2012). The molecular architecture of the eukaryotic chaperonin TRiC/CCT. Structure, 20(5), 814-825. https://doi.org/10.1016/j.str.2012.03.007

The molecular architecture of the eukaryotic chaperonin TRiC/CCT. / Leitner, Alexander; Joachimiak, Lukasz A.; Bracher, Andreas; Mönkemeyer, Leonie; Walzthoeni, Thomas; Chen, Bryan; Pechmann, Sebastian; Holmes, Susan; Cong, Yao; Ma, Boxue; Ludtke, Steve; Chiu, Wah; Hartl, F. Ulrich; Aebersold, Ruedi; Frydman, Judith.

In: Structure, Vol. 20, No. 5, 09.05.2012, p. 814-825.

Research output: Contribution to journalArticle

Leitner, A, Joachimiak, LA, Bracher, A, Mönkemeyer, L, Walzthoeni, T, Chen, B, Pechmann, S, Holmes, S, Cong, Y, Ma, B, Ludtke, S, Chiu, W, Hartl, FU, Aebersold, R & Frydman, J 2012, 'The molecular architecture of the eukaryotic chaperonin TRiC/CCT', Structure, vol. 20, no. 5, pp. 814-825. https://doi.org/10.1016/j.str.2012.03.007
Leitner A, Joachimiak LA, Bracher A, Mönkemeyer L, Walzthoeni T, Chen B et al. The molecular architecture of the eukaryotic chaperonin TRiC/CCT. Structure. 2012 May 9;20(5):814-825. https://doi.org/10.1016/j.str.2012.03.007
Leitner, Alexander ; Joachimiak, Lukasz A. ; Bracher, Andreas ; Mönkemeyer, Leonie ; Walzthoeni, Thomas ; Chen, Bryan ; Pechmann, Sebastian ; Holmes, Susan ; Cong, Yao ; Ma, Boxue ; Ludtke, Steve ; Chiu, Wah ; Hartl, F. Ulrich ; Aebersold, Ruedi ; Frydman, Judith. / The molecular architecture of the eukaryotic chaperonin TRiC/CCT. In: Structure. 2012 ; Vol. 20, No. 5. pp. 814-825.
@article{fded949255af429da1824a0501b2595b,
title = "The molecular architecture of the eukaryotic chaperonin TRiC/CCT",
abstract = "TRiC/CCT is a highly conserved and essential chaperonin that uses ATP cycling to facilitate folding of approximately 10{\%} of the eukaryotic proteome. This 1 MDa hetero-oligomeric complex consists of two stacked rings of eight paralogous subunits each. Previously proposed TRiC models differ substantially in their subunit arrangements and ring register. Here, we integrate chemical crosslinking, mass spectrometry, and combinatorial modeling to reveal the definitive subunit arrangement of TRiC. In vivo disulfide mapping provided additional validation for the crosslinking-derived arrangement as the definitive TRiC topology. This subunit arrangement allowed the refinement of a structural model using existing X-ray diffraction data. The structure described here explains all available crosslink experiments, provides a rationale for previously unexplained structural features, and reveals a surprising asymmetry of charges within the chaperonin folding chamber.",
author = "Alexander Leitner and Joachimiak, {Lukasz A.} and Andreas Bracher and Leonie M{\"o}nkemeyer and Thomas Walzthoeni and Bryan Chen and Sebastian Pechmann and Susan Holmes and Yao Cong and Boxue Ma and Steve Ludtke and Wah Chiu and Hartl, {F. Ulrich} and Ruedi Aebersold and Judith Frydman",
year = "2012",
month = "5",
day = "9",
doi = "10.1016/j.str.2012.03.007",
language = "English (US)",
volume = "20",
pages = "814--825",
journal = "Structure with Folding & design",
issn = "0969-2126",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - The molecular architecture of the eukaryotic chaperonin TRiC/CCT

AU - Leitner, Alexander

AU - Joachimiak, Lukasz A.

AU - Bracher, Andreas

AU - Mönkemeyer, Leonie

AU - Walzthoeni, Thomas

AU - Chen, Bryan

AU - Pechmann, Sebastian

AU - Holmes, Susan

AU - Cong, Yao

AU - Ma, Boxue

AU - Ludtke, Steve

AU - Chiu, Wah

AU - Hartl, F. Ulrich

AU - Aebersold, Ruedi

AU - Frydman, Judith

PY - 2012/5/9

Y1 - 2012/5/9

N2 - TRiC/CCT is a highly conserved and essential chaperonin that uses ATP cycling to facilitate folding of approximately 10% of the eukaryotic proteome. This 1 MDa hetero-oligomeric complex consists of two stacked rings of eight paralogous subunits each. Previously proposed TRiC models differ substantially in their subunit arrangements and ring register. Here, we integrate chemical crosslinking, mass spectrometry, and combinatorial modeling to reveal the definitive subunit arrangement of TRiC. In vivo disulfide mapping provided additional validation for the crosslinking-derived arrangement as the definitive TRiC topology. This subunit arrangement allowed the refinement of a structural model using existing X-ray diffraction data. The structure described here explains all available crosslink experiments, provides a rationale for previously unexplained structural features, and reveals a surprising asymmetry of charges within the chaperonin folding chamber.

AB - TRiC/CCT is a highly conserved and essential chaperonin that uses ATP cycling to facilitate folding of approximately 10% of the eukaryotic proteome. This 1 MDa hetero-oligomeric complex consists of two stacked rings of eight paralogous subunits each. Previously proposed TRiC models differ substantially in their subunit arrangements and ring register. Here, we integrate chemical crosslinking, mass spectrometry, and combinatorial modeling to reveal the definitive subunit arrangement of TRiC. In vivo disulfide mapping provided additional validation for the crosslinking-derived arrangement as the definitive TRiC topology. This subunit arrangement allowed the refinement of a structural model using existing X-ray diffraction data. The structure described here explains all available crosslink experiments, provides a rationale for previously unexplained structural features, and reveals a surprising asymmetry of charges within the chaperonin folding chamber.

UR - http://www.scopus.com/inward/record.url?scp=84861102204&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84861102204&partnerID=8YFLogxK

U2 - 10.1016/j.str.2012.03.007

DO - 10.1016/j.str.2012.03.007

M3 - Article

C2 - 22503819

AN - SCOPUS:84861102204

VL - 20

SP - 814

EP - 825

JO - Structure with Folding & design

JF - Structure with Folding & design

SN - 0969-2126

IS - 5

ER -