|Heat shock 70 kDa protein 1A|
Existing structural: , , , ,
|Properties of human protein|
|Mass / length primary structure||641 amino acids; 70 kDa|
Hsp70 (Hsp stands for heat shock protein ) are a group of proteins and enzymes that help some other proteins in protein folding or in the unfolding of a protein before membrane transport . Hsp70 with a mass of 70 kDa represent an important component of the chaperone system that occurs in eukaryotic cells , in eubacteria and in many archaea .
At least three cytosolic isoforms of the Hsp70 family exist in E. coli , of which DnaK is the best known representative. In eukaryotes , Hsp70 proteins were found in the cytosol, chloroplasts , mitochondria and in the lumen of the endoplasmic reticulum (ER). In archaea, Hsp70 occurs in halophiles and in some, but not all, methanogens . So it is missing z. B. the extremely thermophilic Methanococcos jannaschii . In mammals there are two isoforms in the cytoplasm , a 73 kDa form, which is constitutively expressed (Hsc70), and a stress-inducible, 72 kDa form (Hsp70). This illustrates the general principle that isoforms which are constitutively expressed under physiological conditions exercise some important functions, whereas inducible isoforms of Hsp70 exercise important functions under stress conditions. More recent studies also postulate extracellular localized Hsp70, which could play a key role in the induction of the cellular immune response .
Structural properties of Hsp70
Hsp70 proteins generally consist of a 44 kDa amino terminal ATPase domain and a 28 kDa carboxy terminal domain, which can be divided into an 18 kDa peptide binding domain and a 10 kDa carboxy terminal variable domain with an unknown function.
The Hsp70 ATPase activity
Hsp70 proteins work ATP- dependently on the folding of polypeptide chains. Cycles of substrate binding and release are coupled with ATP binding, hydrolysis and nucleotide exchange. In the ATP-bound form, eukaryotic Hsp70 has a low affinity for substrate proteins, while in the ADP-bound form it has a high affinity for the substrate. Thus, ATP hydrolysis leads to a more stable interaction of Hsp70 with the respective substrate.
Function of Hsp70
The molecular chaperones , such as Hsp70 and Hsp90 , are responsible for the correct folding and activation of many proteins. Hsp70 assists in the folding of a significant proportion of all newly synthesized proteins. One mechanism of this activity is that Hsp70, together with its cochaperone Hsp40 (called DnaK and DnaJ in bacteria), binds to amino acid chains and prevents them from aggregating before they have assumed their correct structure. Hsp70 can also form a multichaperone complex with Hsp90, in which both are linked by a third protein (Hop). The interplay and interaction of these two chaperone machines is of great importance for the survival of cells and organisms ( autophagocytosis ). The importance of these proteins becomes clear from the involvement of Hsp70 proteins in important cellular processes, such as the transport of proteins across membranes , the disassembly of clathrin- enveloped vesicles and the regulation of the heat shock response .
Medical significance of Hsp70
The low molecular weight component 15-Deoxyspergualin (DSG) was discovered as an Hsc70 binding reagent. DSG binds Hsc70 with moderate affinity and stimulates its ATPase activity. This allows therapeutic effects to be achieved. DSG has been observed to reduce the body's rejection response to new tissue in transplant patients . This is explained by the fact that DSG indirectly causes macrophages to be inhibited in their function and cytolytic T and B cells to be disturbed in their proliferation .
13 Hsp70 proteins are known in humans:
|Genname||Protein name||Synonyms||localization||NCBI entry|
|HSPA1A||Hsp70-1a||Hsp70; Hsp70-1; Hsp72; Hsx70||Nucleus / cytosol / lysosome||GeneID 3303|
|HSPA1B||Hsp70-1b||Hsp70-2||Nucleus / cytosol / lysosome||GeneID 3304|
|HSPA1L||Hsp70-1L||hum70t; Hsp70t, Hsp70-hom||Nucleus / cytosol||GeneID 3305|
|HSPA2||Hsp70-2A||HspA2; Hsp70-3||Nucleus / cytosol||GeneID 3306|
|HSPA5||Hsp70-5||BiP; Grp78; MIF2||HE||GeneID 3309|
|HSPA6||Hsp70-6||Hsp70B '; Heat shock 70kD protein 6||Nucleus / cytosol||GeneID 3310|
|HSPA7||Hsp70-7||Hsp70-7; Hsp70B||GeneID 3311|
|HSPA8||Hsp70-8||Hsc70; Hsc71; Hsp71; Hsp73||Nucleus / cytosol||GeneID 3312|
|HSPA9||Hsp70-9||Grp75; mtHSP75; mtHsp70; HspA9B; MOT||Mitochondrion||GeneID 3313|
|HSPA14||Hsp70-14||Hsp70-4; Hsp70L1||GeneID 51182|
Simple organisms such as Escherichia coli have fewer Hsp70 proteins:
|Genname||Protein name||Synonyms||NCBI entry|
|dnak||DnaK||GroPAB; GroPC; GroPF; GrpC; GrpF||GeneID 944750|
- Tavaria, M. et al. (1996): A hitchhiker's guide to the human Hsp70 family . In: Cell Stress Chaperones 1 (1); 23-28; PMID 9222585 , PMC 313013 (free full text)
- Daugaard, M. et al . (2007): The heat shock protein 70 family: Highly homologous proteins with overlapping and distinct functions . In: FEBS Lett . 581 (19); 3702-3710; PMID 17544402 ; doi : 10.1016 / j.febslet.2007.05.039
- H. Wegele, L. Muller, J. Buchner (2004) Hsp70 and Hsp90 - a relay team for protein folding. In: Rev Physiol Biochem Pharmacol , 151: 1-44