6nr9

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hTRiC-hPFD Class5hTRiC-hPFD Class5

Structural highlights

6nr9 is a 22 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[TCPE_HUMAN] Hereditary sensory and autonomic neuropathy with spastic paraplegia. The disease is caused by mutations affecting the gene represented in this entry.

Function

[TCPZ_HUMAN] Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis (PubMed:25467444). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). The TRiC complex plays a role in the folding of actin and tubulin (Probable).[1] [PFD3_HUMAN] Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins.[2] [TCPG_HUMAN] Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis (PubMed:25467444). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). The TRiC complex plays a role in the folding of actin and tubulin (Probable).[3] [4] [TCPH_HUMAN] Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis (PubMed:25467444). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). The TRiC complex plays a role in the folding of actin and tubulin (Probable).[5] [PFD1_HUMAN] Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins. [PFD4_HUMAN] Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins.[6] [TCPB_HUMAN] Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis (PubMed:25467444). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). The TRiC complex plays a role in the folding of actin and tubulin (Probable).[7] [8] [PFD6_HUMAN] Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins.[9] [TCPQ_HUMAN] Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis (PubMed:25467444). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). The TRiC complex plays a role in the folding of actin and tubulin (Probable).[10] [11] [TCPA_HUMAN] Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis (PubMed:25467444). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). The TRiC complex plays a role in the folding of actin and tubulin (Probable).[12] [13] [TCPD_HUMAN] Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis (PubMed:25467444). The TRiC complex mediates the folding of WRAP53/TCAB1, thereby regulating telomere maintenance (PubMed:25467444). As part of the TRiC complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia (PubMed:20080638). The TRiC complex plays a role in the folding of actin and tubulin (Probable).[14] [15] [PFD5_HUMAN] Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins. Represses the transcriptional activity of MYC.[16] [PFD2_HUMAN] Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins.[17] [TCPE_HUMAN] Molecular chaperone; assists the folding of proteins upon ATP hydrolysis. As part of the BBS/CCT complex may play a role in the assembly of BBSome, a complex involved in ciliogenesis regulating transports vesicles to the cilia. Known to play a role, in vitro, in the folding of actin and tubulin.[18]

Publication Abstract from PubMed

Maintaining proteostasis in eukaryotic protein folding involves cooperation of distinct chaperone systems. To understand how the essential ring-shaped chaperonin TRiC/CCT cooperates with the chaperone prefoldin/GIMc (PFD), we integrate cryoelectron microscopy (cryo-EM), crosslinking-mass-spectrometry and biochemical and cellular approaches to elucidate the structural and functional interplay between TRiC/CCT and PFD. We find these hetero-oligomeric chaperones associate in a defined architecture, through a conserved interface of electrostatic contacts that serves as a pivot point for a TRiC-PFD conformational cycle. PFD alternates between an open "latched" conformation and a closed "engaged" conformation that aligns the PFD-TRiC substrate binding chambers. PFD can act after TRiC bound its substrates to enhance the rate and yield of the folding reaction, suppressing non-productive reaction cycles. Disrupting the TRiC-PFD interaction in vivo is strongly deleterious, leading to accumulation of amyloid aggregates. The supra-chaperone assembly formed by PFD and TRiC is essential to prevent toxic conformations and ensure effective cellular proteostasis.

The Chaperonin TRiC/CCT Associates with Prefoldin through a Conserved Electrostatic Interface Essential for Cellular Proteostasis.,Gestaut D, Roh SH, Ma B, Pintilie G, Joachimiak LA, Leitner A, Walzthoeni T, Aebersold R, Chiu W, Frydman J Cell. 2019 Apr 18;177(3):751-765.e15. doi: 10.1016/j.cell.2019.03.012. Epub 2019 , Apr 4. PMID:30955883[19]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

  1. ↑ Freund A, Zhong FL, Venteicher AS, Meng Z, Veenstra TD, Frydman J, Artandi SE. Proteostatic control of telomerase function through TRiC-mediated folding of TCAB1. Cell. 2014 Dec 4;159(6):1389-403. doi: 10.1016/j.cell.2014.10.059. Epub 2014 Nov , 20. PMID:25467444 doi:http://dx.doi.org/10.1016/j.cell.2014.10.059
  2. ↑ Vainberg IE, Lewis SA, Rommelaere H, Ampe C, Vandekerckhove J, Klein HL, Cowan NJ. Prefoldin, a chaperone that delivers unfolded proteins to cytosolic chaperonin. Cell. 1998 May 29;93(5):863-73. PMID:9630229
  3. ↑ Seo S, Baye LM, Schulz NP, Beck JS, Zhang Q, Slusarski DC, Sheffield VC. BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly. Proc Natl Acad Sci U S A. 2010 Jan 4. PMID:20080638 doi:http://dx.doi.org/0910268107
  4. ↑ Freund A, Zhong FL, Venteicher AS, Meng Z, Veenstra TD, Frydman J, Artandi SE. Proteostatic control of telomerase function through TRiC-mediated folding of TCAB1. Cell. 2014 Dec 4;159(6):1389-403. doi: 10.1016/j.cell.2014.10.059. Epub 2014 Nov , 20. PMID:25467444 doi:http://dx.doi.org/10.1016/j.cell.2014.10.059
  5. ↑ Freund A, Zhong FL, Venteicher AS, Meng Z, Veenstra TD, Frydman J, Artandi SE. Proteostatic control of telomerase function through TRiC-mediated folding of TCAB1. Cell. 2014 Dec 4;159(6):1389-403. doi: 10.1016/j.cell.2014.10.059. Epub 2014 Nov , 20. PMID:25467444 doi:http://dx.doi.org/10.1016/j.cell.2014.10.059
  6. ↑ Vainberg IE, Lewis SA, Rommelaere H, Ampe C, Vandekerckhove J, Klein HL, Cowan NJ. Prefoldin, a chaperone that delivers unfolded proteins to cytosolic chaperonin. Cell. 1998 May 29;93(5):863-73. PMID:9630229
  7. ↑ Seo S, Baye LM, Schulz NP, Beck JS, Zhang Q, Slusarski DC, Sheffield VC. BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly. Proc Natl Acad Sci U S A. 2010 Jan 4. PMID:20080638 doi:http://dx.doi.org/0910268107
  8. ↑ Freund A, Zhong FL, Venteicher AS, Meng Z, Veenstra TD, Frydman J, Artandi SE. Proteostatic control of telomerase function through TRiC-mediated folding of TCAB1. Cell. 2014 Dec 4;159(6):1389-403. doi: 10.1016/j.cell.2014.10.059. Epub 2014 Nov , 20. PMID:25467444 doi:http://dx.doi.org/10.1016/j.cell.2014.10.059
  9. ↑ Vainberg IE, Lewis SA, Rommelaere H, Ampe C, Vandekerckhove J, Klein HL, Cowan NJ. Prefoldin, a chaperone that delivers unfolded proteins to cytosolic chaperonin. Cell. 1998 May 29;93(5):863-73. PMID:9630229
  10. ↑ Seo S, Baye LM, Schulz NP, Beck JS, Zhang Q, Slusarski DC, Sheffield VC. BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly. Proc Natl Acad Sci U S A. 2010 Jan 4. PMID:20080638 doi:http://dx.doi.org/0910268107
  11. ↑ Freund A, Zhong FL, Venteicher AS, Meng Z, Veenstra TD, Frydman J, Artandi SE. Proteostatic control of telomerase function through TRiC-mediated folding of TCAB1. Cell. 2014 Dec 4;159(6):1389-403. doi: 10.1016/j.cell.2014.10.059. Epub 2014 Nov , 20. PMID:25467444 doi:http://dx.doi.org/10.1016/j.cell.2014.10.059
  12. ↑ Seo S, Baye LM, Schulz NP, Beck JS, Zhang Q, Slusarski DC, Sheffield VC. BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly. Proc Natl Acad Sci U S A. 2010 Jan 4. PMID:20080638 doi:http://dx.doi.org/0910268107
  13. ↑ Freund A, Zhong FL, Venteicher AS, Meng Z, Veenstra TD, Frydman J, Artandi SE. Proteostatic control of telomerase function through TRiC-mediated folding of TCAB1. Cell. 2014 Dec 4;159(6):1389-403. doi: 10.1016/j.cell.2014.10.059. Epub 2014 Nov , 20. PMID:25467444 doi:http://dx.doi.org/10.1016/j.cell.2014.10.059
  14. ↑ Seo S, Baye LM, Schulz NP, Beck JS, Zhang Q, Slusarski DC, Sheffield VC. BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly. Proc Natl Acad Sci U S A. 2010 Jan 4. PMID:20080638 doi:http://dx.doi.org/0910268107
  15. ↑ Freund A, Zhong FL, Venteicher AS, Meng Z, Veenstra TD, Frydman J, Artandi SE. Proteostatic control of telomerase function through TRiC-mediated folding of TCAB1. Cell. 2014 Dec 4;159(6):1389-403. doi: 10.1016/j.cell.2014.10.059. Epub 2014 Nov , 20. PMID:25467444 doi:http://dx.doi.org/10.1016/j.cell.2014.10.059
  16. ↑ Vainberg IE, Lewis SA, Rommelaere H, Ampe C, Vandekerckhove J, Klein HL, Cowan NJ. Prefoldin, a chaperone that delivers unfolded proteins to cytosolic chaperonin. Cell. 1998 May 29;93(5):863-73. PMID:9630229
  17. ↑ Vainberg IE, Lewis SA, Rommelaere H, Ampe C, Vandekerckhove J, Klein HL, Cowan NJ. Prefoldin, a chaperone that delivers unfolded proteins to cytosolic chaperonin. Cell. 1998 May 29;93(5):863-73. PMID:9630229
  18. ↑ Seo S, Baye LM, Schulz NP, Beck JS, Zhang Q, Slusarski DC, Sheffield VC. BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly. Proc Natl Acad Sci U S A. 2010 Jan 4. PMID:20080638 doi:http://dx.doi.org/0910268107
  19. ↑ Gestaut D, Roh SH, Ma B, Pintilie G, Joachimiak LA, Leitner A, Walzthoeni T, Aebersold R, Chiu W, Frydman J. The Chaperonin TRiC/CCT Associates with Prefoldin through a Conserved Electrostatic Interface Essential for Cellular Proteostasis. Cell. 2019 Apr 18;177(3):751-765.e15. doi: 10.1016/j.cell.2019.03.012. Epub 2019 , Apr 4. PMID:30955883 doi:http://dx.doi.org/10.1016/j.cell.2019.03.012

6nr9, resolution 8.50Å

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