Biology:Hop (protein)

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

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).

Synonyms

Hop Hsc70/Hsp90-organizing protein NY-REN-11 antigen P60

STI1 STI1L STIP1 Transformation-sensitive protein IEF-SSP-3521

Gene

The gene for human Hop is located on chromosome 11q13.1 and consists of 14 exons.

Structure

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 ligand peptides.

The Hsp70-Hsp90 Organizing Protein (Hop, STIP1 in humans) is the co-chaperone responsible for the transfer of client proteins between Hsp70 and Hsp90. Hop is evolutionarily conserved in Eukaryotes and is found in both the nucleus and cytoplasm. Drosophila Hop is a monomeric protein that consists of three tetratricopeptide repeat domain regions (TPR1, TPR2A, TPR2B), one aspartic acid-proline repeat domain (DP). The TPR domains interact with the c-terminals of Hsp90 and Hsp70, with TPR1 and TPR2B binding to Hsp70 and TPR2A binding preferentially to Hsp90. The intermediate structures of heat shock machinery are difficult to characterize completely because of the transient and fast paced nature of chaperone function.

Function

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.

In Drosophila RNA interference pathways, Hop has been shown to be an integral part of the pre-RISC complex for siRNAs. In the Drosophila Piwi-interacting RNA pathway, the RNA interference pathway responsible for the repression of transposable elements (transposons), Hop has been shown to interact with Piwi, and in the absence of Hop, transposons are derepressed, leading to severe genomic instability and infertility.

Interactions

Human Hop (STIP1) has been shown to interact with PRNP and Heat shock protein 90kDa alpha (cytosolic), member A1.

Further reading

• "Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes". Electrophoresis 13 (12): 960–9. December 1992. doi:10.1002/elps.11501301199. PMID 1286667. 
• "Molecular cloning and expression of a transformation-sensitive human protein containing the TPR motif and sharing identity to the stress-inducible yeast protein STI1". The Journal of Biological Chemistry 267 (12): 8485–91. April 1992. doi:10.1016/S0021-9258(18)42471-4. PMID 1569099. 
• "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. January 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
• "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research 6 (9): 791–806. September 1996. doi:10.1101/gr.6.9.791. PMID 8889548. 
• "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". The Journal of Biological Chemistry 272 (20): 13047–54. May 1997. doi:10.1074/jbc.272.20.13047. PMID 9148915. 
• "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". The Journal of Biological Chemistry 272 (34): 21213–20. August 1997. doi:10.1074/jbc.272.34.21213. PMID 9261129. 
• "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. October 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
• "Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1". Cell 94 (4): 471–80. August 1998. doi:10.1016/S0092-8674(00)81588-3. PMID 9727490. 
• "Antigens recognized by autologous antibody in patients with renal-cell carcinoma". International Journal of Cancer 83 (4): 456–64. November 1999. doi:10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5. PMID 10508479. 
• "Structure of TPR domain-peptide complexes: critical elements in the assembly of the Hsp70-Hsp90 multichaperone machine". Cell 101 (2): 199–210. April 2000. doi:10.1016/S0092-8674(00)80830-2. PMID 10786835. 
• "HSP40 binding is the first step in the HSP90 chaperoning pathway for the progesterone receptor". The Journal of Biological Chemistry 277 (14): 11873–81. April 2002. doi:10.1074/jbc.M111445200. PMID 11809754. 
• "Ligand discrimination by TPR domains. Relevance and selectivity of EEVD-recognition in Hsp70 x Hop x Hsp90 complexes". The Journal of Biological Chemistry 277 (22): 19265–75. May 2002. doi:10.1074/jbc.M109002200. PMID 11877417. 
• "Stress-inducible protein 1 is a cell surface ligand for cellular prion that triggers neuroprotection". The EMBO Journal 21 (13): 3307–16. July 2002. doi:10.1093/emboj/cdf325. PMID 12093732. 
• "The assembly and intermolecular properties of the hsp70-Hop-hsp90 molecular chaperone complex". The Journal of Biological Chemistry 277 (41): 38294–304. October 2002. doi:10.1074/jbc.M206566200. PMID 12161444. 
• "The Hsp90 co-chaperones Cdc37 and Sti1 interact physically and genetically". Biological Chemistry 383 (9): 1335–42. September 2002. doi:10.1515/BC.2002.152. PMID 12437126. 
• "A product of the human gene adjacent to parkin is a component of Lewy bodies and suppresses Pael receptor-induced cell death". The Journal of Biological Chemistry 278 (51): 51901–10. December 2003. doi:10.1074/jbc.M309655200. PMID 14532270. 
• "Nuclear translocation of the Hsp70/Hsp90 organizing protein mSTI1 is regulated by cell cycle kinases". Journal of Cell Science 117 (Pt 5): 701–10. February 2004. doi:10.1242/jcs.00905. PMID 14754904. 
• "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells". Nature Biotechnology 23 (1): 94–101. January 2005. doi:10.1038/nbt1046. PMID 15592455.