Hsp70

  • MGI: 96244

Hsp70 proteins ( Hsp stands for heat shock protein) represent an important component of the chaperone system, which is found ubiquitously in eukaryotic cells, in eubacteria and in many archaea.

In E. coli, there are at least three isoforms of cytosolic Hsp70 family, of which DnaK is the most famous representative. In eukaryotes are Hsp70 proteins in the cytosol, have been found in chloroplasts, mitochondria, and in the lumen of the endoplasmic reticulum (ER). In archaea Hsp70 comes in Halo -philes and in some, but not all, methanogens ago. For example jannaschii the extremely thermophilic Methanococcos is missing. In mammals, two isoforms exist 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 under physiological conditions constitutively expressed isoforms exert some important functions, whereas exercise inducible isoforms of Hsp70 important functions under stress conditions. Recent studies postulate extracellularly localized Hsp70, which could play a key role in the induction of 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, the 18 kDa peptide-binding domain and a 10 kDa carboxy-terminal variable domain can be divided into an unknown function.

Hsp70 -ATPase activity

Hsp70 proteins function ATP - dependent in the folding of polypeptide chains. Cycles of substrate binding and release are coupled to ATP binding and hydrolysis nucleotide. In the form of ATP bound eukaryotic Hsp70 has a low affinity for substrate proteins, while it has a high affinity in the form of ADP bound to the substrate. Thus therefore 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 proper folding and activation of many proteins. Hsp70 assists in the folding of a significant proportion of all newly synthesized proteins. A mechanism of this activity is that Hsp70, together with his Cochaperon Hsp40 ( DnaK and DnaJ in bacteria called ) binds to amino acid chains and prevents them from aggregating before they have accepted their correct structure. Hsp70 may also form with a Multichaperonkomplex Hsp90, in which both of a third protein ( hop ) are connected. The interaction and the interaction of these two Chaperonmaschinen is of high importance for the survival of cells and organisms ( autophagy ). Characterized in that Hsp70 proteins in important cellular processes such as the transport of proteins through membranes, the disassembly of clathrin- coated vesicles and regulation of the heat shock response is involved, the importance of this protein is clear.

Medical importance 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. As a result, therapeutic effects can be achieved. It has been observed that DSG reduces the rejection response of the body to a new tissue in transplant patients. This explains it by the fact that DSG indirectly result that macrophages inhibited in their function and cytolytic T- and B- cells are disrupted in proliferation.

Survey

In humans, 13 Hsp70 proteins are known:

Simple organisms, such as Escherichia coli, have proteins of less Hsp70:

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