TITLE

The architecture of functional modules in the Hsp90 co-chaperone Sti1/Hop

AUTHOR(S)
Schmid, Andreas B; Lagleder, Stephan; Gräwert, Melissa Ann; Röhl, Alina; Hagn, Franz; Wandinger, Sebastian K; Cox, Marc B; Demmer, Oliver; Richter, Klaus; Groll, Michael; Kessler, Horst; Buchner, Johannes
PUB. DATE
March 2012
SOURCE
EMBO Journal;3/21/2012, Vol. 31 Issue 6, p1506
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Sti1/Hop is a modular protein required for the transfer of client proteins from the Hsp70 to the Hsp90 chaperone system in eukaryotes. It binds Hsp70 and Hsp90 simultaneously via TPR (tetratricopeptide repeat) domains. Sti1/Hop contains three TPR domains (TPR1, TPR2A and TPR2B) and two domains of unknown structure (DP1 and DP2). We show that TPR2A is the high affinity Hsp90-binding site and TPR1 and TPR2B bind Hsp70 with moderate affinity. The DP domains exhibit highly homologous ?-helical folds as determined by NMR. These, and especially DP2, are important for client activation in vivo. The core module of Sti1 for Hsp90 inhibition is the TPR2A-TPR2B segment. In the crystal structure, the two TPR domains are connected via a rigid linker orienting their peptide-binding sites in opposite directions and allowing the simultaneous binding of TPR2A to the Hsp90 C-terminal domain and of TPR2B to Hsp70. Both domains also interact with the Hsp90 middle domain. The accessory TPR1-DP1 module may serve as an Hsp70-client delivery system for the TPR2A-TPR2B-DP2 segment, which is required for client activation in vivo.
ACCESSION #
73523345

 

Related Articles

  • A Dynamic View of ATP-coupled Functioning Cycle of Hsp90 N-terminal Domain. Zhang, Huaqun; Zhou, Chen; Shi, Yanhong; Wen, Yi; Chen, Wuyan; Xu, Yechun; Zhang, Naixia // Scientific Reports;4/10/2015, p9542 

    Heat-shock protein 90 (Hsp90) is one of the most important chaperones involved in multiple cellular processes. The chaperoning function of Hsp90 is intimately coupled to the ATPase activity presented by its N-terminal domain. However, the molecular mechanism for the ATP-dependent working cycle...

  • NMR and Mutational Identification of the Collagen-Binding Site of the Chaperone Hsp47. Yagi-Utsumi, Maho; Yoshikawa, Sumi; Yamaguchi, Yoshiki; Nishi, Yohei; Kurimoto, Eiji; Ishida, Yoshihito; Homma, Takayuki; Hoseki, Jun; Nishikawa, Yoshimi; Koide, Takaki; Nagata, Kazuhiro; Kato, Koichi; Driscoll, Paul C. // PLoS ONE;Sep2012, Vol. 7 Issue 9, Special section p1 

    Heat shock protein 47 (Hsp47) acts as a client-specific chaperone for collagen and plays a vital role in collagen maturation and the consequent embryonic development. In addition, this protein can be a potential target for the treatment of fibrosis. Despite its physiological and pathological...

  • Crystal Structure of the Stress-Inducible Human Heat Shock Protein 70 Substrate-Binding Domain in Complex with Peptide Substrate. Zhang, Pingfeng; Leu, Julia I-Ju; Murphy, Maureen E.; George, Donna L.; Marmorstein, Ronen // PLoS ONE;Jul2014, Vol. 9 Issue 7, p1 

    The HSP70 family of molecular chaperones function to maintain protein quality control and homeostasis. The major stress-induced form, HSP70 (also called HSP72 or HSPA1A) is considered an important anti-cancer drug target because it is constitutively overexpressed in a number of human cancers and...

  • Identification of the pentapeptide constituting a dominant epitope common to all eukaryotic heat shock protein 90 molecular chaperones. Kishimoto, Jun; Fukuma, Yutaka; Mizuno, Akio; Nemoto, Takayuki K. // Cell Stress & Chaperones;Winter2005, Vol. 10 Issue 4, p296 

    We previously reported that, in human heat shock protein (Hsp) 90 (hHsp90), there are 4 highly immunogenic sites, designated sites la, Ib, Ic, and II. This study was performed to further characterize their epitopes and to identify the epitope that is potentially common to all members of the...

  • Characterization of rice small heat shock proteins targeted to different cellular organelles. Mani, Nandini; Ramakrishna, Krishnaveni; Suguna, Kaza // Cell Stress & Chaperones;May2015, Vol. 20 Issue 3, p451 

    Small heat shock proteins (sHSPs) are a family of ATP-independent molecular chaperones which prevent cellular protein aggregation by binding to misfolded proteins. sHSPs form large oligomers that undergo drastic rearrangement/dissociation in order to execute their chaperone activity in...

  • Differential conformational dynamics in the closely homologous FK506-binding domains of FKBP51 and FKBP52. MUSTAFI, Sourajit M.; LEMASTER, David M.; ÁNDEZ, Griselda HERN // Biochemical Journal;7/1/2014, Vol. 461 Issue 1, preceding p115 

    As co-chaperones of Hsp90 (heat-shock protein 90), FKBP51 (FK506-binding protein of 51 kDa) and FKBP52 (FK506-binding protein of 52 kDa) act as antagonists in regulating the hormone affinity and nuclear transport of steroid receptor complexes. Exchange of Leu119 in FKBP51 for Pro119 in FKBP52...

  • Crystal structure of the Psb27 assembly factor at 1.6 Ã…: implications for binding to Photosystem II. Michoux, Franck; Takasaka, Kenji; Boehm, Marko; Komenda, Josef; Nixon, Peter; Murray, James // Photosynthesis Research;Feb2012, Vol. 110 Issue 3, p169 

    The biogenesis and oxygen-evolving activity of cyanobacterial Photosystem II (PSII) is dependent on a number of accessory proteins not found in the crystallised dimeric complex. These include Psb27, a small lipoprotein attached to the lumenal side of PSII, which has been assigned a role in...

  • Phage display biopanning identifies the translation initiation and elongation factors (IF1α-3 and eIF-3) as components of Hsp70-peptide complexes in breast tumour cells. Siebke, Christina; James, Tharappel; Cummins, Robert; O'Grady, Tony; Kay, Elaine; Bond, Ursula // Cell Stress & Chaperones;Summer2012, Vol. 17 Issue 2, p145 

    The heat shock protein, HSP70, is over-expressed in many tumours and acts at the crossroads of key intracellular processes in its role as a molecular chaperone. HSP70 associates with a vast array of peptides, some of which are antigenic and can mount adaptive immune responses against the tumour...

  • Heat Shock Proteins (HSPs): a Review. Tkáčová, Jana; Angelovičová, Mária // Scientific Papers: Animal Science & Biotechnologies / Lucrari St;Jan2012, Vol. 45 Issue 1, p349 

    Heat shock proteins (HSPs) are a large class of proteins that have been conserved throughout evolution and exist by prokaryote and eukaryote organisms. Heat shock proteins play an important role in protein homeostasis. They can found in all major cellular compartments. The HSP90 family are...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics