Small heat shock proteins

Small heat shock proteins (Engl. Small heat shock proteins , short sHsps) are proteins with molecular masses of 12-42  kDa , which occur in all living things. They belong to the family of heat shock proteins , which are increasingly formed during heat and other cellular stressful situations. Small heat shock proteins are molecular chaperones that bind non-native substrate proteins. In this way, they prevent possible irreversible protein aggregation and thus contribute to the fact that proteins during chemical or physical stress conditions, e.g. B. during a heat shock. In humans nine sHsps are confirmed; Mutations in their genes are responsible for several rare hereditary diseases (see table).

protein	Gene (HGNC)	UniProt	Length (AA)	pathology
Heat shock protein β-1	HSPB1	P04792	205	Charcot-Marie-Tooth disease type 2F; Hereditary motor-sensitive neuropathy type 2B
Heat shock protein β-2	HSPB2	Q16082	182
Heat shock protein β-3	HSPB3	Q12988	150	Hereditary motor-sensitive neuropathy type 2C
α-Crystallin A chain	CRYAA	P02489	173	Hereditary cataract
α-Crystallin B chain	CRYAB	P02511	175	Myopathy (MFM2); Hereditary cataract ; Congenital Muscular Dystrophy (MFMFIH-CRYAB)
Heat shock protein β-6	HSPB6	O14558	160
Heat shock protein β-7	HSPB7	Q9UBY9	170
Heat shock protein β-8	HSPB8	Q9UJY1	196	Charcot-Marie-Tooth disease type 2L; Hereditary motor-sensitive neuropathy type 2A
Heat shock protein β-9	HSPB9	Q9BQS6	159

Also unconfirmed:

• ODFP1 ( sperm outer dense fiber protein ) (HSPB10)
• HSPB11

construction

The conserved structural feature of all sHsps - the so-called alpha-crystallin domain - was named because of its similarity to α-A / B-crystallin. α-A / B-Crystallin are important human eye lens proteins. This conserved, C-terminal domain is typically 80 to 100 amino acids long and is the characteristic feature of this protein family. The folding motif consists of β-sheets and its topology is similar to the so-called immunoglobulin folding motif (see antibodies ).

Both the N-terminal domain and the short C-terminal end of the sHsps are not conserved in sequence or length and vary considerably between the individual representatives. For α-crystallin and murine HSP25 it was shown by NMR measurements that the C-terminal extensions are flexible. Some sHSPs have phosphorylation sites. Human HSP27 is e.g. B. phosphorylated at serines in different positions in the protein (S15, S78 and S82).

Small heat shock proteins form oligomers of up to 800 kDa. In HSP27, oligomerization appears to be regulated by phosphorylation. Smaller oligomers of HSP27 appear to have a cytoskeletal stabilizing function, while large oligomers have a chaperone function.

function

The sHsps are similar in their structure and biological function. The functions of the small heat shock proteins include protection against programmed cell death ( apoptosis ), stabilization of the cell skeleton ( cytoskeleton ) and the support of the correct folding of other proteins ( chaperone function ). Some representatives of the sHsps are phosphoproteins that are phosphorylated by members of the MAPKAPK family.

Some bacteria have no or only one sHSP.

literature

• Cap, G et al. (2003): The human genome encodes 10 alpha-crystallin-related small heat shock proteins: HspB1-10 . In: Cell Stress Chaperones 8 (1): 53-61. PMID 12820654 , PMC 514853 (free full text)
• Haslbeck, M. et al. (2005): Some like it hot: the structure and function of small heat-shock proteins . In: Nat Struct Mol Biol. 12 (10); 842-6. PMID 16205709

Individual evidence

1. ↑ H. Kleinig, U. Maier: Kleinig / custom - Cell Biology , 4th edition, Gustav Fischer Verlag 1999, ISBN 3-437-26010-3 .
2. ↑ Jakob, U. et al. (1993). Small heat shock proteins are molecular chaperones . In: J Biol Chem 268 (3), 1517-20; PMID 8093612 , PDF (free full text access ).
3. ↑ Haslbeck, M. et al. (1999). Hsp26: a temperature-regulated chaperone . In: EMBO J . 18 (23), 6744-51; PMID 10581247 ; PMC 1171736 (free full text)
4. ↑ Bellyei, S. et al. (2002): Inhibition of cell death by a novel 16.2 kD heat shock protein predominantly via Hsp90 mediated lipid rafts stabilization and Akt activation pathway . In: Apoptosis. 2007 (12) , 97-112.
5. ↑ Kappé, G. et al. (2002): Evolution and diversity of prokaryotic small heat shock proteins . In: Prog Mol Subcell Biol. 28 , 1-17, PMID 11908054 .