6nr8

<table><tr><td colspan='2'>[[6nr8]] is a 22 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NR8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6NR8 FirstGlance]. <br>

</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PFDN1, PFD1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CCT4, CCTD, SRB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CCT5, CCTE, KIAA0098 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CCT6A, CCT6, CCTZ ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CCT7, CCTH, NIP7-1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CCT8, C21orf112, CCTQ, KIAA0002 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PFDN2, PFD2, HSPC231 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), VBP1, PFDN3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PFDN4, PFD4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PFDN5, MM1, PFD5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PFDN6, HKE2, PFD6 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), TCP1, CCT1, CCTA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CCT2, 99D8.1, CCTB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CCT3, CCTG, TRIC5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6nr8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nr8 OCA], [http://pdbe.org/6nr8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nr8 RCSB], [http://www.ebi.ac.uk/pdbsum/6nr8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nr8 ProSAT]</span></td></tr>

== Disease ==

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

[[http://www.uniprot.org/uniprot/PFD6_HUMAN 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.<ref>PMID:9630229</ref> [[http://www.uniprot.org/uniprot/TCPE_HUMAN 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.<ref>PMID:20080638</ref> [[http://www.uniprot.org/uniprot/PFD3_HUMAN 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.<ref>PMID:9630229</ref> [[http://www.uniprot.org/uniprot/TCPA_HUMAN 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).<ref>PMID:20080638</ref> <ref>PMID:25467444</ref> [[http://www.uniprot.org/uniprot/TCPG_HUMAN 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).<ref>PMID:20080638</ref> <ref>PMID:25467444</ref> [[http://www.uniprot.org/uniprot/PFD2_HUMAN 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.<ref>PMID:9630229</ref> [[http://www.uniprot.org/uniprot/TCPZ_HUMAN 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).<ref>PMID:25467444</ref> [[http://www.uniprot.org/uniprot/TCPQ_HUMAN 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).<ref>PMID:20080638</ref> <ref>PMID:25467444</ref> [[http://www.uniprot.org/uniprot/TCPB_HUMAN 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).<ref>PMID:20080638</ref> <ref>PMID:25467444</ref> [[http://www.uniprot.org/uniprot/PFD1_HUMAN 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. [[http://www.uniprot.org/uniprot/PFD4_HUMAN 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.<ref>PMID:9630229</ref> [[http://www.uniprot.org/uniprot/TCPD_HUMAN 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).<ref>PMID:20080638</ref> <ref>PMID:25467444</ref> [[http://www.uniprot.org/uniprot/TCPH_HUMAN 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).<ref>PMID:25467444</ref> [[http://www.uniprot.org/uniprot/PFD5_HUMAN 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.<ref>PMID:9630229</ref>

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.

 

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== References ==

[[Category: Human]]

[[Category: Aebersold, R]]

[[Category: Chiu, W]]

[[Category: Frydman, J]]

[[Category: Gestaut, D R]]

[[Category: Joachimiak, L A]]

[[Category: Leitner, A]]

[[Category: Ma, B]]

[[Category: Pintilie, G]]

[[Category: Roh, S H]]

[[Category: Walzthoeni, T]]

[[Category: Tric/cct]]