Chaperonin—Co-chaperonin Interactions - The Networking of Chaperones by Co-chaperones - page 152

GroEL and its co-chaperonin GroES are the quintessential members of this fam-
ily of protein folding machines (Hartl and Hayer-Hartl 2002 ; Hartl 1996 ; Horwich
et al. 2007 ). Hemmingsen first used the term 'chaperonin' (Cpn) in 1988 to repre-
sent this family of molecular chaperones (Hemmingsen et al. 1988 ). The Hsp60
family of chaperones is one of the most abundant classes of molecular chaperone
present in the plastids, mitochondria, and cytoplasm of all eukaryotes and eubacte-
ria. GroEL, the only essential molecular chaperone in E. coli , is indispensable for
viability at all temperatures (Fayet et al. 1989 ; Ang and Georgopoulos 1989 ) and S.
cerevisiae is non-viable without CCT subunits (Stoldt et al. 1996 ). Mitochondrial
Hsp60 inactivation results in embryonic lethality in mice (Christensen et al. 2010 ).
The terms GroEL and GroES were initially applied strictly to the two proteins
found in E. coli and have been extended to include homologues from other bacte-
rial species. The GroEL protein functions as a typical molecular chaperone as it
binds and folds proteins, whilst GroES exhibits no autonomous role as a chaperone
but modulates the activity of GroEL and is referred to as a co-chaperone. The term
chaperonin is applied to bacterial proteins that are homologous to the E. coli GroEL
and are also referred to as Cpn60, whilst co-chaperonins refer to homologues of E.
coli GroES, also known as Cpn10. Whilst the mitochondrial homologues are called
Hsp60 and Hsp10, the archeal chaperonins are referred to as thermosomes (Trent
et al. 1991 ). In the eukaryotic group, chaperonins found in the cytosol were first
called TCP-1 and are now also called CCT (chaperonin containing TCP-1) (Kubota
et al. 1994 ), TRiC (TCP containing ring complex) (Frydman et al. 1992 ) and c-cpn
(Gao et al. 1992 ). The human HSP60/HSP10 proteins have been renamed HSPD/E
(Kampinga et al. 2009 ). The chloroplast chaperonin is referred to as Cpn60 protein,
whilst two types of co-chaperonins Cpn10 and Cpn20 are present (Koumoto et al.
2001 ). Prior to its recognition as chloroplast Cpn60, it was known as Rubisco bind-
ing protein (Barraclough and Ellis 1980 ).
The chaperonins share a common subunit organisation and structure. They are
a family of ATPases consisting of twin heptameric rings stacked back-to-back to
create a characteristic cylindrical structure and function by assisting in the folding
of nascent and misfolded proteins (Hartl and Martin 1995 ; Houry et al. 1999 ). Each
ring creates a large cavity for unfolded proteins to bind and undergo productive fold-
ing to the native state in a highly cooperative and ATP-dependent manner (Bukau
and Horwich 1998 ; Hartl and Hayer-Hartl 2002 ). Co-chaperonins form a single
heptameric ring of 10 kDa subunits and are present in all bacterial and eukaryotic
organisms (Hartl 1996 ). The E. coli GroEL/GroES complex consists of two stacked
heptameric rings of GroEL capped by a single heptameric ring of GroES that forms
the lid over the folding cage (Fig. 8.1 ). The functional cycle requires the binding
of chaperonin 10 to one or both chaperonin rings which forms a lid-like structure
on top of the cyclinder when ATP is bound that causes the chamber to enlarge to
allow for protein folding (Chandrasekhar et al. 1986 ; Saibil 1996 ). A vital part of
the structure of each subunit is a flexible mobile loop that mediates binding to the
chaperonin (Landry et al. 1996 ). The flexibility and the structure of the complex is
conserved amongst co-chaperonins and sequence variations impose differences in
binding affinity (Richardson et al. 2001 ). Protein substrates first bind to the apical