Page 387 - Carrahers_Polymer_Chemistry,_Eighth_Edition

350 Carraher’s Polymer Chemistry

today in science. To the synthetic polymer chemist, understanding the influences, the basics

or fundamentals, which produce protein chain folding will allow the creation of new synthetic

polymers that possess specifically desired properties. For biochemists, understanding these fac-
tors allows us to better understand other factors and to combat particular diseases related to
chain folding.
The particular shape of protein chains is known as a fold and the process is called chain folding.
While chain folding is often referred to as a self-assembly process, it also involves other specialized
separate proteins that assist in this chain folding so it is not truly self-assembly. Chain folding occurs
rapidly in the time scale of 1–10 millionths of a second or tens of microseconds.
Chain folding depends on the primary and secondary structures of materials. Thus, the particu-
lar atomic composition of a chain dictates, under equilibrium conditions, its tertiary and quaternary
structures.
Proteins act as structural and “enzyme-type” materials. Much of the present discussion focuses
on the folding of enzyme-type materials, but it is equally applicable to structural proteins. While
the human genome has less than about 30,000 genes, these genes account for as many as one mil-
lion proteins most of these being nonstructural in nature. Proteins also undergo maturing, or to be
more truthful, aging, as it carries out its function(s). As with much of nature, after extended use and
associated damage related to chemical and partial unfolding, the protein is degraded and its parts
often becoming part of a newly synthesized protein.
As already noted, protein folding is dependent on the primary chemical structure. Chain folding
begins even as it is being synthesized by ribosomes. The assembly area is crowed with this crowding

increasing the risk of nonspecific association and aggregation. A primary driving force for aggrega-

tion is simply the push to bury hydrophobic portions of the molecule away from the influences of the
hydrophilic, water-rich, birthing surrounding. Thus, left to itself, folded proteins have a hydrophilic
surface that contains within it the more hydrophobic portions. But this tendency must be moderated
or simple aggregation of the hydrophobic and hydrophilic portions, ribbons, occurs and even worse,
unwanted aggregation of the proteins themselves occurs.
Crowding is one factor that is not easily achieved away from the native environment. Lack of
crowding is one of the major reasons why in vivo and in vitro syntheses often result in proteins with
different activities.
While we characterize nonstructural proteins as being globular in shape, these shapes vary con-
siderably according to their use. Again, this overall shape is governed by a combination of factors,
including primary and secondary structure.
A family of proteins assists in the folding process of proteins in general. These proteins are
called molecular chaperones. As in the case of a date, the chaperones help guide appropriate inter-
actions and discourage unwanted associations. Chaperones are found in all of our cells. Many of
them are designated by the acronym Hsp for heat shock protein. They are also designated by the
relative mass in kilodaltons so that a Hsp70 means it is a chaperone molecule that is about 70 kDa
in mass. The main chaperones are Hsp60 (chaperonins), Hsp70, and Hsp90.
Typically, a series of steps is involved in the work carried out by chaperone molecules. Hsp70
operates on the protein as it is being formed on the ribosome. It recognizes extended or exposed pro-
tein chain regions that are more hydrophobic and acts to discourage unwanted association of these
parts. It also acts to maintain the growing protein in a somewhat unfolded state.
Hsp70 hands off the protein to another class of chaperones known as Hsp60 or simply chap-
eronins. Chaperonins create a protected environment sometimes known as an “Anfi nsen cage”
because it creates an enclosed environment where the protein segments spontaneously fold, free
from aggregating with other proteins and somewhat free from aqueous infl uences. These are large
proteins that are somewhat cylindrical in shape. Chaperonins are composed of two major units,
stacked rings.
There are two different classes of chaperonins. Class I includes eukaryotic cells and class II
includes certain prokaryotic cells. Eukaryotic cells have nuclei and include our cells. Prokaryotic

9/14/2010 3:41:23 PM
K10478.indb 350 9/14/2010 3:41:23 PM
K10478.indb 350