Chaperonin—Co-chaperonin Interactions - The Networking of Chaperones by Co-chaperones - page 166

The structure of human mitochondrial Hsp10 has been solved and mutations in
the first and last ʲ-strands altered both the oligomeric and folded states (Guidry
et al. 2003 ). In contrast to human mitochondrial Hsp60, Hsp10 stimulates the pro-
duction of anti-inflammatory cytokines and exerts immunosuppressive activity
(Johnson et al. 2005 ). One of the first extracellular heat shock proteins to be isolated
was a circulating immunosuppressive protein, termed early pregnancy factor (EPF),
which was later identified as HSP10 (HSPE) after the isolation and demonstration
of its role as a co-chaperonin for Hsp60 (Cavanagh and Morton 1994 ; Morton et al.
1977 ). The isolation of EPF was also the first evidence that heat shock proteins
could function as cell signalling agonists (Morton et al. 1977 ). EFP appeared in the
maternal serum within 24 h after fertilisation in some mammalians and has been
found to exhibit growth factor qualities and anti-inflammatory properties essen-
tial for protecting the embryo from the mother's own immune system (Athanasas-
Platsis et al. 2004 ; Morton et al. 1977 ; Quinn et al. 1990 ). The relationship between
Hsp10 and EPF is discussed in a review by (Corrao et al. 2010 ). Recombinant hu-
man Hsp10 has been used for the treatment of rheumatoid arthritis (Vanags et al.
2006 ) and multiple sclerosis (Broadley et al. 2009 ). Extracellular Hsp10 influences
endothelial cell differentiation (Dobocan et al. 2009 ). There is growing evidence to
suggest that extracellular Hsp10 plays an active role in cell signalling (David et al.
2013 ). A number of reviews have been written on Hsp60 chaperonopathies, diseases
that arise from abnormal chaperonins (Cappello et al. 2008 ; Cappello et al. 2013 ;
Cappello et al. 2011 ; Cappello et al. 2014 ; Macario and Conway de Macario 2005 ,
2007 ).
Conclusion
Continued research on the influence of the cellular environment on the GroEL/ES
folding machine and factors affecting the rate of protein folding will enhance our
understanding of this system. The evolution of moonlighting functions of bacte-
rial chaperonins and co-chaperonins needs to be addressed. The structural states of
Hsp10, including mixed oligomeric or fragmented, appears to influence the func-
tion as well as location. Hsp10 often functions as an antagonist to Hsp60 and pos-
sibly other molecular chaperones. Further knowledge of the extracellular functions
of Hsp10, including secretion pathways and cell signalling, will definitely be of
benefit in the development of treatments for cancer and auto-immune diseases re-
lated to this protein.
Acknowledgments Financial support from the National Research Foundation (NRF), Rhodes
University and Deutsche Forschungsgemeinschaft (DFG) is gratefully acknowledged. The views
reflected in this document are those of the author and should in no way be attributed to the NRF,
Rhodes University or DFG.