Hop, occasionally written HOP, is an abbreviation for Hsp70-Hsp90 Organizing Protein. It functions as a co-chaperone which reversibly links together the protein chaperones Hsp70 and Hsp90.
Hop belongs to the large group of co-chaperones, which regulate and assist the major chaperones (mainly heat shock proteins). It is one of the best studied co-chaperones of the Hsp70/Hsp90-complex. It was first discovered in yeast and homologues were identified in human, mouse, rat, insects, plants, parasites, and virus. The family of these proteins is referred to as STI1 (stress inducible protein) and can be divided into yeast, plant, and animal STI1 (Hop).
The gene for human Hop is located on chromosome 11q13.1 and consists of 14 exons.
STI proteins are characterized by some structural features: All homologues have nine tetratricopeptide repeat (TPR) motifs, that are clustered into domains of three TPRs. The TPR motif is a very common structural feature used by many proteins and provides the ability of directing protein-protein interactions. Crystallographic structural information is available for the N-terminal TPR1 and the central TPR2A domains in complex with Hsp90 resp. Hsp70 ligandpeptides.
The main function of Hop is to link Hsp70 and Hsp90 together. But recent investigations indicate that it also modulates the chaperone activities of the linked proteins and possibly interacts with other chaperones and proteins. Apart from its role in the Hsp70/Hsp90 "chaperone machine" it seems to participate in other protein complexes too (for example in the signal transduction complex EcR/USP and in the Hepatitis B virus reverse transcriptase complex, which enables the viral replication). It acts as a receptor for prion proteins too. Hop is located in diverse cellular regions and also moves between the cytoplasm and the nucleus.
^Scheufler, C; Brinker A, Bourenkov G, Pegoraro S, Moroder L, Bartunik H, Hartl F U, Moarefi I (April 2000). "Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine". Cell (UNITED STATES) 101 (2): 199–210. doi:10.1016/S0092-8674(00)80830-2. ISSN0092-8674. PMID10786835.Cite uses deprecated parameters (help)
^Johnson, B D; Schumacher R J, Ross E D, Toft D O (February 1998). "Hop modulates Hsp70/Hsp90 interactions in protein folding". J. Biol. Chem. (UNITED STATES) 273 (6): 3679–86. doi:10.1074/jbc.273.6.3679. ISSN0021-9258. PMID9452498.Cite uses deprecated parameters (help)
Rasmussen HH, van Damme J, Puype M, et al. (1993). "Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes". Electrophoresis13 (12): 960–9. doi:10.1002/elps.11501301199. PMID1286667.
Honoré B, Leffers H, Madsen P, et al. (1992). "Molecular cloning and expression of a transformation-sensitive human protein containing the TPR motif and sharing identity to the stress-inducible yeast protein STI1". J. Biol. Chem.267 (12): 8485–91. PMID1569099.
Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res.6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID8889548.
Dittmar KD, Pratt WB (1997). "Folding of the glucocorticoid receptor by the reconstituted Hsp90-based chaperone machinery. The initial hsp90.p60.hsp70-dependent step is sufficient for creating the steroid binding conformation". J. Biol. Chem.272 (20): 13047–54. doi:10.1074/jbc.272.20.13047. PMID9148915.
Dittmar KD, Demady DR, Stancato LF, et al. (1997). "Folding of the glucocorticoid receptor by the heat shock protein (hsp) 90-based chaperone machinery. The role of p23 is to stabilize receptor.hsp90 heterocomplexes formed by hsp90.p60.hsp70". J. Biol. Chem.272 (34): 21213–20. doi:10.1074/jbc.272.34.21213. PMID9261129.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Zou J, Guo Y, Guettouche T, et al. (1998). "Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1". Cell94 (4): 471–80. doi:10.1016/S0092-8674(00)81588-3. PMID9727490.
Scheufler C, Brinker A, Bourenkov G, et al. (2000). "Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine". Cell101 (2): 199–210. doi:10.1016/S0092-8674(00)80830-2. PMID10786835.
Hernández MP, Chadli A, Toft DO (2002). "HSP40 binding is the first step in the HSP90 chaperoning pathway for the progesterone receptor". J. Biol. Chem.277 (14): 11873–81. doi:10.1074/jbc.M111445200. PMID11809754.
Brinker A, Scheufler C, Von Der Mulbe F, et al. (2002). "Ligand discrimination by TPR domains. Relevance and selectivity of EEVD-recognition in Hsp70 x Hop x Hsp90 complexes". J. Biol. Chem.277 (22): 19265–75. doi:10.1074/jbc.M109002200. PMID11877417.
Hernández MP, Sullivan WP, Toft DO (2002). "The assembly and intermolecular properties of the hsp70-Hop-hsp90 molecular chaperone complex". J. Biol. Chem.277 (41): 38294–304. doi:10.1074/jbc.M206566200. PMID12161444.
Abbas-Terki T, Briand PA, Donzé O, Picard D (2003). "The Hsp90 co-chaperones Cdc37 and Sti1 interact physically and genetically". Biol. Chem.383 (9): 1335–42. doi:10.1515/BC.2002.152. PMID12437126.
Imai Y, Soda M, Murakami T, et al. (2004). "A product of the human gene adjacent to parkin is a component of Lewy bodies and suppresses Pael receptor-induced cell death". J. Biol. Chem.278 (51): 51901–10. doi:10.1074/jbc.M309655200. PMID14532270.
Longshaw VM, Chapple JP, Balda MS, et al. (2004). "Nuclear translocation of the Hsp70/Hsp90 organizing protein mSTI1 is regulated by cell cycle kinases". J. Cell. Sci.117 (Pt 5): 701–10. doi:10.1242/jcs.00905. PMID14754904.