CHAPTER
Three-Dimensional Structure
of Proteins
Proteins that consist of a single polypeptide chain are gen-
erally considered at three levels of organization:
primary,
secondary,
and
tertiary structure.
For proteins that con-
tain two or more polypeptide chains, each chain is a subunit
and there is a
quaternary
level of structure. The primary
structure is the unique sequence of amino acids that make
up a particular polypeptide; primary structure is main-
tained by covalent bonds; secondary, tertiary, and quater-
nary structures are maintained principally by noncovalent
bonds; disulfide bridges may also be considered at the
secondary and tertiary levels. Secondary structure arises
from repeated hydrogen bonding within a chain, as in the
a-helix, (3-pleated sheet,
and
/3-turns
(discussed later).
Tertiary structure describes the three-dimensional stereo-
chemical relationships of all of the amino acid residues
in a single protein chain.
Folding
of a polypeptide is an
orderly sequential process by which the polypeptide at-
tains the lowest possible state of energy. The folding of
the polypeptide into its secondary structure is determined
primarily by the primary structure. Once the secondary
structures are in place, a tertiary structure is formed and
stabilized by interactions among amino acids which may
be far from each other in the primary sequence but which
are close to each other in the three-dimensional structure.
In a discussion of protein structure, it is necessary to
differentiate the terms “configuration” and “conforma-
tion.”
Configuration
refers to the absolute arrangement of
atoms or substituent groups in space around a given atom.
Configurational isomers cannot be interconverted with-
out breaking one or more covalent bonds. For example,
D and L-amino acids (Chapter 2), which have different
amino acid configurations around the asymmetrical car-
bon atom, are not interconvertible without the breaking
and remaking of one or more covalent bonds.
Conforma-
tion
refers to a three-dimensional arrangement of groups
of atoms that can be altered without breaking any covalent
bonds. For example, rotation around single bonds allows
molecules to undergo transitions between conformational
isomers (conformers), as in the eclipsed and staggered
conformers of ethane (Figure 4-1). Since rotation is rel-
atively unrestricted around the H
3
C-CH
3
bond, the two
conformers rapidly interconvert.
Proteins contain many single bonds capable of free ro-
tation. Theoretically, therefore, proteins can assume an
infinite number of possible conformations but under nor-
mal biological conditions, they assume only one or a very
small number of “most stable” conformations. Proteins
depend upon these stable conformations for their specific
biological functions. A functional protein is said to be in
its
native
form, usually the most stable one. The three-
dimensional conformation of a polypeptide chain is ulti-
mately determined by its amino acid sequence (primary
structure). Changes in that sequence, as they arise from
mutations in DNA, may yield conformationally altered
(and often less stable, less active, or inactive) proteins.
Since the biological function of a protein depends on a
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