Small heat shock proteins (sHSPs) as potential drug targets.
Small heat shock proteins (sHSPs) belong to a family of 12- to 43-kDa proteins that are ubiquitous and are largely conserved in amino acid sequence among all organisms. The principal heat-shock proteins that have chaperone activity (that is, they protect newly made proteins from misfolding) belong to five conserved classes: HSP100, HSP90, HSP70, HSP60 and the small heat-shock proteins (sHSPs). The sHSPs (which include alpha crystallin) can form large multimeric structures and have a wide range of cellular functions, including endowing cells with thermotolerance in vivo and being able to act as molecular chaperones in vitro; sHSPs do this by forming stable complexes with folding -or unfolding--intermediates of their protein substrates, probably the molten globule. This paper includes: a brief survey of the chaperone family, the small heat shock protein superfamily, transcription of sHSPs, sequence comparisons and structural models of small heat shock proteins--structural elements as potential drug targets, sHSPs as chaperone-like proteins, alpha crystallin chaperone-like activity, conformational diseases--the role of alpha crystallin small heat shock protein superfamily proteins, post-translational modification and useful pharmacological agents. Functionality of small heat shock proteins--targets and diseases where pharmacologically active agents are of importance, alpha crystallin--small heat shock proteins and prion diseases: specific targets for diagnostic tests and drug development, details of some specific small heat shock proteins as drug targets, structural and functional implications for treatment.
James
M
M
Division of Cell and Molecular Biology, School of Animal and Microbial Sciences, The University of Reading, Berkshire, UK. m.j.c.crabbe@reading.ac.uk
Crabbe
C
C
Hepburne-Scott
H W
HW
D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D006360:Heat-Shock Proteins / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D008970:Molecular Weight
D006360:Heat-Shock Proteins