Hsp70

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Heat shock 70 kDa protein 1A

Existing structural data : 1hjo , 1s3x , 1xqa , 2e88 , 2e8a

Properties of human protein
Mass / length primary structure 641 amino acids; 70  kDa
Cofactor ATP
Isoforms SNPs, deletion
Identifier
Gene name HSPA1A
External IDs
Occurrence
Parent taxon Creature
Orthologue
human mouse
Entrez 3303 193740
Ensemble ENSG00000204389 ENSMUSG00000067283
UniProt P08107 Q61696
Refseq (mRNA) NM_005345 NM_010479
Refseq (protein) NP_005337 NP_034609
Gene locus Chr 6: 3.03 - 3.03 Mb Chr 17: 35.11 - 35.11 Mb
PubMed search 3303 193740

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 .

properties

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 .

Overview

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
HSPA12A Hsp70-12a GeneID 259217
HSPA12B Hsp70-12b GeneID 116835
HSPA13 Hsp70-13 Stch GeneID 6782
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
hscA HscA Hsc66 GeneID 944885
hscC HscC Hsc62 GeneID 945218

Individual evidence

  1. ↑ 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)
  2. ↑ 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

literature

See also