loading...| Preferred Name |
Protein Folding |
|
| Synonyms |
PathwayType: signaling Organ: generic Pathway_Author: A. Nesterova ORCID:0000-0002-9448-8101 Organ_System: generic Tissue: generic Notes: Headnote: Most proteins need to be folded into a certain three-dimensional structure to fulfill their biological functions. Some proteins have been shown to fold spontaneously, but many newly synthesized proteins require the assistance of molecular chaperones to reach their folded states efficiently. Signaling description: The role of chaperones is largely to optimize the efficiency of folding rather than to deliver steric information to the folding process. The chaperone pathways operate in the endoplasmic reticulum. Heat shock proteins HSPA8, HSPA1A, and HSPA14 are the central organizers of the chaperone network and distribute subsets of proteins to chaperones that act downstream including chaperonins (TRiC) and HSP90AA1. ATP binding causes the release of the substrate which allows folding toward the native state to proceed. Approximately 20% of chains reach their native states in a reaction assisted by HSPA14 and DnaJ family proteins. Initially, ribosome-bound chaperones HSPA14 directly bind to the large ribosomal subunit in close proximity to the polypeptide exit site. The DnaJ family interacts directly with unfolded polypeptides and can recruit heat shock 70kDa proteins to protein substrates. Several polypeptides fold with the assistance of HSPA14, whereas others are passed to HSP90AA1. Around 10% of the chains are passed on to the TRiC co- or post-translationally. The chaperonins are large, cylindrical complexes that function by enclosing protein molecules so that folding can occur unimpaired by aggregation. TRiC interacts directly with HSPA8 and other upstream factors such as prefoldin. The family of co-chaperones containing modular TPR clamp domains, including ST13, FKBP4, and UNC45A, organize the transfer of proteins from HSPA14 to HSP90AA1. Some mitochondrial precursor proteins are delivered by HSPA1A and HSP90AA1 to TOMM70A for import into the mitochondria. Outcome effects: The ubiquitin-ligase STUB1 contacts heat shock 70kDa and 90kDa proteins to attach polyubiquitin onto substrate polypeptides for degradation. NodeType: Pathway Description: Most proteins need to be folded into a certain three-dimensional structure to fulfill their biological functions. Pathway is built manually using published studies. Link: https://mammal-profservices.pathwaystudio.com/app/sd?urn=urn:agi-pathway:uuid-aa559429-3701-4071-ad0c-6086182e5cc0 Source: Cell Process CellType: generic |
|
| ID |
urn:agi-pathway:uuid-aa559429-3701-4071-ad0c-6086182e5cc0 |
|
| database_cross_reference |
PS:PathwayType PS:Description PS:Tissue PS:Pathway_Author PS:Link PS:CellType PS:Organ_System PS:NodeType PS:Notes PS:Organ PS:Source |
|
| has_exact_synonym |
PathwayType: signaling Organ: generic Pathway_Author: A. Nesterova ORCID:0000-0002-9448-8101 Organ_System: generic Tissue: generic Notes: Headnote: Most proteins need to be folded into a certain three-dimensional structure to fulfill their biological functions. Some proteins have been shown to fold spontaneously, but many newly synthesized proteins require the assistance of molecular chaperones to reach their folded states efficiently. Signaling description: The role of chaperones is largely to optimize the efficiency of folding rather than to deliver steric information to the folding process. The chaperone pathways operate in the endoplasmic reticulum. Heat shock proteins HSPA8, HSPA1A, and HSPA14 are the central organizers of the chaperone network and distribute subsets of proteins to chaperones that act downstream including chaperonins (TRiC) and HSP90AA1. ATP binding causes the release of the substrate which allows folding toward the native state to proceed. Approximately 20% of chains reach their native states in a reaction assisted by HSPA14 and DnaJ family proteins. Initially, ribosome-bound chaperones HSPA14 directly bind to the large ribosomal subunit in close proximity to the polypeptide exit site. The DnaJ family interacts directly with unfolded polypeptides and can recruit heat shock 70kDa proteins to protein substrates. Several polypeptides fold with the assistance of HSPA14, whereas others are passed to HSP90AA1. Around 10% of the chains are passed on to the TRiC co- or post-translationally. The chaperonins are large, cylindrical complexes that function by enclosing protein molecules so that folding can occur unimpaired by aggregation. TRiC interacts directly with HSPA8 and other upstream factors such as prefoldin. The family of co-chaperones containing modular TPR clamp domains, including ST13, FKBP4, and UNC45A, organize the transfer of proteins from HSPA14 to HSP90AA1. Some mitochondrial precursor proteins are delivered by HSPA1A and HSP90AA1 to TOMM70A for import into the mitochondria. Outcome effects: The ubiquitin-ligase STUB1 contacts heat shock 70kDa and 90kDa proteins to attach polyubiquitin onto substrate polypeptides for degradation. NodeType: Pathway Description: Most proteins need to be folded into a certain three-dimensional structure to fulfill their biological functions. Pathway is built manually using published studies. Source: Cell Process CellType: generic |
|
| id |
urn:agi-pathway:uuid-aa559429-3701-4071-ad0c-6086182e5cc0 |
|
| label |
Protein Folding |
|
| notation |
uuid-aa559429-3701-4071-ad0c-6086182e5cc0 |
|
| prefLabel |
Protein Folding |
|
| treeView |
urn:agi-folder:endoplasmic_reticulum urn:agi-folder:golgi_apparatus urn:agi-folder:generic urn:agi-folder:p urn:agi-folder:proteins_turnover |
|
| subClassOf |
urn:agi-folder:endoplasmic_reticulum urn:agi-folder:golgi_apparatus urn:agi-folder:generic urn:agi-folder:p urn:agi-folder:proteins_turnover |