(mentions CMT) Structure, properties, and functions of the human small heat-shoc

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J Neurosci Res. 2007 Aug 24

Structure, properties, and functions of the human small heat-shock

protein HSP22 (HspB8, H11, E2IG1): A critical review.

Shemetov AA, Seit-Nebi AS, Gusev NB.

Department of Biochemistry, School of Biology, Moscow State

University, Moscow, Russia.

The recently described human HSP22 belongs to the superfamily of

small heat-shock proteins containing a conservative alpha-crystallin

domain. HSP22 seems to be involved in regulation of cell

proliferation, cardiac hypertrophy, apoptosis, and carcinogenesis,

and expression of point mutants of HSP22 correlates with development

of different neuromuscular diseases. Therefore, an investigation of

the structure and properties of HSP22 is desirable for understanding

its multiple functions.

HSP22 seems to belong to the group of so-called intrinsically

disordered proteins and possesses a highly flexible structure. HSP22

tends to form small-molecular-mass oligomers and interacts with

biological membranes and many different proteins, among them

glycolytic enzymes and different protein kinases. HSP22 possesses

chaperonelike activity and prevents aggregation of denatured

proteins both in vitro and in vivo.

Depending on the cell type and its expression, HSP22 might have

either pro- or anti-apoptotic effects. Chaperonelike activity seems

to be important for antiapoptotic effects, whereas interaction with

and regulation of certain protein kinases might be important for the

proapoptotic effects of HSP22. Expression of K141N or K141E mutants

of HSP22 correlates with development of distal hereditary motor

neuropathy and/or Charcot-Marie-Tooth disease.

These mutations destabilize the structure of HSP22, affect its

interaction with other small heat-shock proteins, and decrease its

chaperonelike activity. HSP22 decreases or prevents aggregation of

Huntingtin fragments and amyloid-beta peptide 1-40 of the Dutch

type. Thus, HSP22 seems to play an important role in the nervous

system, and further investigations are needed to understand the

molecular mechanisms of its functioning.