Chaperonin—Co-chaperonin Interactions - The Networking of Chaperones by Co-chaperones - page 154

Chandra et al. 2007 ). The roles played by both intracellular and extracellular forms
of human HSP10 (HSPE) in pregnancy, cancer and autoimmune diseases continue
to receive attention (Jia et al. 2011 ; Corrao et al. 2010 ).
Whilst the E. coli chaperonins are encoded by only two genes, groEL and groES ,
both Cpn60 and Cpn10 found in green algae and plants are encoded by numerous
genes (Boston et al. 1996 ; Hill and Hemmingsen 2001 ; Schroda 2004 ). The com-
plexity of chloroplast chaperonins has been viewed by (Vitlin Gruber et al. 2013a ).
It also appears that approximately 30 % of bacteria encode more than one groEL
gene (Hill and Hemmingsen 2001 ). The biological significance of several chapero-
nin genes has yet to be revealed (Lund 2009 ), however the literature has expanded
in recent years in this area of research. In general, it appears as though major sub-
units play housekeeping roles and minor subunits have more specialised functions
and fold specific proteins (Peng et al. 2011 ).
The chaperonins can be further sub-divided into two distantly related groups.
Group I chaperonins are found in eubacteria, mitochondria and chloroplasts, of
which GroEL from E. coli is the best studied and understood (Leroux 2001 ). They
form homooligomeric complexes consisting of two stacked heptameric rings togeth-
er with the heptameric Hsp10 co-chaperonin that forms the lid for the folding cage
(Braig et al. 1994 ). Group II chaperonins are present in archaebacteria and in the
eukaryotic cytosol (Horwich et al. 1993 ; Frydman 2001 ). Although both subgroups
form ring-like structures with cavities for sequestered protein folding, Group II
chaperonins form heterooligomeric complexes (Spiess et al. 2004 ; Archibald et al.
1999 ). The Group II chaperonins consist of two eight or nine-membered rings con-
sisting of one to three subunit types in the archeal thermosome rings (Phipps et al.
1991 ), while TRiC/CCT rings consist of eight subunit types (Frydman et al. 1992 ;
Spiess et al. 2004 ). An important difference between the two groups is the lack of a
GroES homologue in the Group II chaperonins (Horwich and Saibil 1998 ). Group
I chaperonins utilize an independently expressed co-chaperonin that functions as a
lid to aid the encapsulation of unfolded protein, whilst Group II chaperonins have
a built-in lid in the form of a particular α-helical protrusion and do not require
additional protein subunits to function (Vabulas et al. 2010 ; Meyer et al. 2003 ).
However, the activity of CCT is regulated by a number of co-chaperones, including
prefoldin, phosducin-like proteins and BAG3 (Vainberg et al. 1998 ; Martin-Benito
et al. 2002 ; Stirling et al. 2006 ; Fontanella et al. 2010 ). In 2010, a third group was
proposed in bacteria and are conserved in the genomes of 11 bacteria (Techtmann
and Robb 2010 ). These novel chaperonins are capable of refolding denatured pro-
teins in a GroES-independant manner. Group III chaperoinins are highly divergent
and distantly related to Group I and Group II and they might represent an ancient
horizontal gene transfer event from archaea to bacteria, and this may revise the cur-
rent paradigm for chaperonin classification (Techtmann and Robb 2010 ).
Over the past 25 years many researchers have demonstrated the abilities of the
E. coli GroEL and GroES machine to bind and refold a wide range of aggregation
prone proteins both in vivo and in vitro . Early in vitro experiments demonstrating