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Naturally Occurring Polymers—Animals 351

cells do not contain nuclei and other organelles. We will focus on eukaryotic cells. Much of the
information we have on chaperonins is derived from studying bacteria such as Escherichia coli.
The chaperonin in E. coli is given the designation GroES–GroEL. The GroEL is composed of two
stacked 7-memebered rings of 60 kDa mass that form a cylinder about 15 nm high and 14 nm wide,
with a 5 nm central cavity capable of holding proteins to 60 kDa. GroES is a cochaperonin that acts
as a dome or cap for one end of the GroEL portion. It is composed of a single 7-membered ring
of about 10 kD mass. Thus, much is know concerning the structures of at least a few of molecules
involved in the folding process. Much is also known concerning the function of these molecules, but
this is beyond the present scope.
Our cells contain about 1%–2% Hsp90 of the total cytosolic proteins. This is a huge percentage
in comparison to most other proteins and signals their importance. Their action depends on the
cyclic binding and hydrolysis of ATP. Hsp90 is involved with conformational regulation of signal
transduction molecules.
Along with the guiding of chaperon molecules there are some “native” or natural tendencies
with respect to chain folding, at least for smaller proteins. One somewhat common sense one but
one only recently described involves the closeness of various segments and folding rate. Briefl y,
protein segments that are located close to one another and in a generally reasonably close orien-

tation to the final folding location promote rapid chain folding. This is reasonable since it takes
more time to organize protein segments that are further from one another relative to organization
of structures that after folding will be close to one another. Even so, not all of what we are fi nding
is the most “reasonable.” For instance, interatomic interactions are not as important as previously
believed. This suggests that local sequences, the primary structures, are most important in deter-

mining the final folded structures and rates at which these structures are achieved. These fi nd-
ings have been found for smaller groups to about 150 units in length. It is not known if they will

be true for larger proteins. At times one tendency may be influenced by other factors. Thus, for
beta-lactoglobulin, the local structure favors a helical structure but this tendency is overcome by
tertiary interactions.
What is known is that we have not yet mastered the art of chain folding. We are aware that several
groups of factors are involved with the folding and more will probably become apparent. We also
know that there is a balance between these factors and again an understanding of factors infl uencing
this balance will also become better know.

An added importance to understanding and being able to influence chain folding involves the
number of diseases that are related to misfolds. For instance, misfolding can result in aggregation of
the proteins, which is a symptom of Mad Cow, Creutzfeldt–Jakob, and Alzheimer’s diseases.
It has been suggested that about 50% of cancers involve some chain misfolding. A key protein
in this is the p53 protein, which exerts tumor suppression. A single DNA strand break can result in
uncontrolled cell division but it normally activates p53 activity, which promotes the production of
other proteins that block cell division or bring about cell death, and thus the cessation of the precan-
cer activity. Mutation of a single nucleotide in p53 is believed to result in a misfold resulting in the
protein’s inability to recognize when it is needed or a failure to act correctly.
Diabetes can involve misfolding of proteins that formed in the endoplasmic reticulum (ER). The
ER secretes certain hormones, enzymes, and antibodies and so is a key player in our health. In some
cases, the misfolded proteins interfere with carbohydrate metabolism leading to diabetes.
Other protein misfolding-associated diseases include lung diseases, including cystic fi brosis and
hereditary emphysema, blood coagulation, certain infectious diseases, and liver diseases. Thus, a
better understanding of chain folding is important to the health of many of us.

10.8 GENETIC ENGINEERING

Genetic engineering is the alteration of an organism’s genetic material. The aim is to introduce into
the organism’s genetic material some desirable trait that is otherwise absent. Alternation of genetic

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