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 language | English (US) |
|---|---|
| Pages (from-to) | 814-825 |
| Number of pages | 12 |
| Journal | Structure |
| Volume | 20 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 9 2012 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Structural Biology
- Molecular Biology
Cite this
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 journal › Article
}
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 -