Page 241 - Color Atlas of Biochemistry
P. 241
232 Organelles
Protein maturation tible to proteinases. To protect partly folded
proteins, there are auxiliary proteins called
After translation, proteins destined for the chaperones because they guard immature
secretory pathway (see p. 228) first have to proteins against damaging contacts. Chaper-
fold into their native conformation within the ones are formed increasingly during tempera-
rER (see p. 230). During this process they are ture stress and are therefore also known as
supported by various auxiliary proteins. heat-shock proteins (hsp). Several classes of
hsp are distinguished. Chaperones of the
hsp70 type (Dna K in bacteria) are common,
A. Protein folding in the rER
as are type hsp60 chaperonins (GroEL/ES in
To prevent incorrect folding of the growing bacteria). Class hsp90 chaperones have spe-
protein during protein biosynthesis, chaper- cial tasks (see p. 378).
ones (see B) inthe lumenof the rER bind to While small proteins canoften reachtheir
the peptide chain and stabilize it until trans- native conformation without any help (1),
lation has been completed. Binding protein larger molecules require hsp70 proteins for
(BiP) is an important chaperone in the ER. protection against aggregation which bind as
Many secretory proteins—e. g., pancreatic monomers and can dissociate again, depend-
ribonuclease (RNAse; see p. 74)—contain sev- ent on ATP (3). By contrast, type hsp60 chap-
eral disulfide bonds that are only formed ox- eronins form large, barrel-shaped complexes
idatively from SH groups after translation. with 14 subunits in which proteins can fold
The eight cysteine residues of the RNAse can independently while shielded from their en-
in principle form 105 different pairings, but vironment (4). The function of hsp60 has been
only the combination of the four disulfide investigated in detail in the bacterial
bonds shown on p. 75 provides active en- chaperonin GroEL (right). The barrel has two
zyme. Incorrect pairings can block further chambers, which are closed with a lid (GroES)
foldingorlead tounstableorinsoluble con- during folding of the guest protein. Driven by
formations. The enzyme protein disulfide iso- ATP hydrolysis, the chambers open and close
merase [1] accelerates the equilibration be- alternately—i. e., the release of the fully folded
tween paired andunpairedcysteineresidues, protein from one chamber is coupled to the
so that incorrect pairs can be quickly split uptake of an unfolded peptide in the second
before the protein finds its final conformation. chamber.
Most peptide bonds in proteins take on the
trans conformation (see p. 66). Only bonds
with proline residues (–X–Pro–) can be C. Protein import in mitochondria
present in both cis and trans forms. Class hsp70 chaperones are also needed for
In the protein’s native conformation, every translocation of nuclear-coded proteins from
X–Pro bond has to have the correct conforma- the cytoplasm into the mitochondria (see
tion (cis or trans). As the uncatalyzed transi- p. 228). As two membranes have to be
tion between the two forms is very slow, crossed to reach the matrix, there are two
there is a proline cis–trans isomerase [2] in translocator complexes: TOM (“transport
the ER that accelerates the conversion. outer membrane”) and TIM (“transport inner
membrane”). For transport, proteins are un-
folded in the cytoplasm and protected by
B. Chaperones and chaperonins
hsp70. TOM recognizes the positively charged
Most proteins fold spontaneously into their signal sequence at the protein’s N terminus
native conformation, even in the test tube. (see p. 228) and with the help of the mem-
In thecell, wherethere arevery high concen- brane potential threads the chains through
–1
trations of proteins (around 350 g L ), this the central pores of the two complexes. Inside
is more dif cult. In the unfolded state, the TIM, further hsp70 molecules bind and pull
apolar regions of the peptide chain (yellow) the chain completely into the matrix. As with
tend to aggregate—due to the hydrophobic import into the ER, the signal peptide is pro-
effect (see p. 28)—with other proteins or teolytically removed by a signal peptidase
with each other to form insoluble products during translocation.
(2). In addition, unfolded proteins are suscep-
Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
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