Molecular Playground/Hsp70-Hsp90
From Proteopedia
| Line 2: | Line 2: | ||
==Hsp70-Hsp90 Organizing Protein (Hop)== | ==Hsp70-Hsp90 Organizing Protein (Hop)== | ||
| - | Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. | + | Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B. |
| + | |||
==TPR Domain 1 Structure== | ==TPR Domain 1 Structure== | ||
| + | TPR1 consists of 3 TPR motifs and is responsible for the interaction | ||
| + | |||
<scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs. | <scene name='User:Lydia_Lamriben/Sandbox1/Erdj5/1'>ERdj5</scene> is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal <scene name='User:Lydia_Lamriben/Sandbox1/J-domain/4'>J-domain</scene> that has been shown to bind to BIP, ER resident HSP70, four redox-active <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin_domains/1'>thioredoxin</scene> domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two <scene name='User:Lydia_Lamriben/Sandbox1/Thioredoxin-like_domains/3'>thioredoxin-like</scene> domains shown in yellow, which lack CXXC redox-active motifs. | ||
Revision as of 21:33, 3 December 2013
|
Contents |
Hsp70-Hsp90 Organizing Protein (Hop)
Hop is an adaptor protein which mediates the association of the molecular chaperones Hsp70 and Hsp90 as some proteins require their coordinated activities for folding and conformational regulation. Hsp90 receives its substrates from Hsp70 in a reaction that is critically dependent on Hop, but how Hop mediates this hand-off was unclear until structural studies of Hop were conducted. Hop is not a chaperone itself, and it is composed almost entirely of Tetra-trico-peptide repeat (TPR) domains. TPR domains are defined as multiple repeats of 34 amino acids that share a degenerate consensus sequence consisting of a pattern of small and large hydrophobic amino acids, with no position being completely invariant. TPR domains are found in many proteins and often serve as interaction modules in multiprotein complexes. Hop is a 543 amino acid protein with 9 predicted TPR motifs, which are organized into 3 TPR domains, TPR1, TPR2A, and TPR2B.
TPR Domain 1 Structure
TPR1 consists of 3 TPR motifs and is responsible for the interaction
is an Endoplasmic Reticulum (ER) resident protein disulfide isomerase. It is a 793 amino acid multi-domain protein. It consists of an N-terminal that has been shown to bind to BIP, ER resident HSP70, four redox-active domains (displayed here in green) and their respective redox-active CXXC motifs labeled in red and two domains shown in yellow, which lack CXXC redox-active motifs.
Function
ERdj5 is believed to play a critical role in ERAD (ER Associated Degradation) in that it is required for reducing ERAD substrates and facilitating their retrotranslocation from the ER to the cytoplasm. It has been shown to interact with EDEM (ER Degradation Enhancing Mannosidase), a protein that recognizes misfolded substrates and targets them for ERAD.
References
1. Hagiwara M. et. al. Molecular Cell; 41. 2011
2. Ushioda R. et. al. Science; 321. 2008
Proteopedia Page Contributors and Editors (what is this?)
Jill Graham, Michal Harel, Eric Martz, Carrie Morrison Penland
