3 The Structural Variety and Metabolism of Proteins
3.1
3.1.1
3.1.2
3.1.3
3.1.4
3.1.5
3.2
3.2.1
3.2.2
3.2.3
Structural Variety
Protein Constituents
Phosphorylation and Dephosphorylation
Analysis and Comparison of Protein Sequences
Folding of the Polypeptide Chain
Multiple Forms of Proteins
Protein Synthesis
Aminoacyl-tRNA Synthetases
Initiation, Elongation and Termination
Transport of Newly Synthesized Proteins to Their
Correct Destinations in the Cell
3.1 Structural Variety
Individual eukaryote cells contain in the order of
10 4 different proteins, and each animal species
contains an even greater number due to differences between the tissues of an individual and
between the individuals themselves; furthermore, the protein spectrum changes during the
course of development. The number of different
proteins to be found in extant organisms may be
as high as 10 12 • The description of this variety, its
origin and biological significance is the most
extensive theme in comparative biochemistry.
This chapter will concern itself with the possibilities for structural variation and the general metabolism of proteins; further chapters will deal with
comparative studies of individual proteins.
3.1.1 Protein Constituents
The primary products of protein biosynthesis are
linear polymers of the 20 standard amino acids.
There has been much speculation about why the
a-amino acids, out of the many possible aminocarbonic acids, should be used in the construction
of proteins; why only those particular 20; and
why only in the L-configuration. Undoubtedly,
this has to do with the changing relationships
between the evolution of amino acid metabolism
3.3
3.3.1
3.3.2
3.3.3
3.3.4
3.3.5
3.4
3.4.1
3.4.2
3.4.3
Proteolysis
Exopeptidases
Serine Proteinases
Cysteine Proteinases
Aspartate Proteinases
Metalloproteinases
Proteinase Inhibitors
Serine-Proteinase Inhibitors
Cysteine-Proteinase Inhibitors
az-Macroglobulins
References
and that of the genetic code, about which there is
as yet no general agreement [245]. The analysis of
amino acid composition is part of the routine
work of the protein chemist, and innumerable
tables of data are now available. Despite the considerable differences between individual proteins,
the spectrum of the protein-bound amino acids
varies much less than that of the free amino acids
(Table 3.1). The number of codons in the genetic
code for individual amino acids varies between
one and six. If each of the 61 amino acid codons
occurred at the same frequency, then each amino
acid would be present in the total protein in proportion to the number of its codons. In actual
fact, lysine, aspartic acid and glutamic acid in particular occur more frequently than would be
expected; arginine, on the other hand, is markedly under-represented. This may be because
arginine appeared as a protein constituent quite
late in evolution (the "intruder hypothesis" of
Jukes), or because a previously larger arginine
fraction has, for some reason, been selected
against in the course of evolution (the "selection
hypothesis" of Wallis), e.g. because the peptide
bonds involving arginine are preferred sites for
protease attack, or the extremely basic property
of arginine, in contrast to lysine, cannot be later
modified by substitution. Although the basic
amino acids arginine and lysine together have
eight co dons and the acidic amino acids aspartic
acid and glutamic acid have only four, they are
3.1
3.1.1
3.1.2
3.1.3
3.1.4
3.1.5
3.2
3.2.1
3.2.2
3.2.3
Structural Variety
Protein Constituents
Phosphorylation and Dephosphorylation
Analysis and Comparison of Protein Sequences
Folding of the Polypeptide Chain
Multiple Forms of Proteins
Protein Synthesis
Aminoacyl-tRNA Synthetases
Initiation, Elongation and Termination
Transport of Newly Synthesized Proteins to Their
Correct Destinations in the Cell
3.1 Structural Variety
Individual eukaryote cells contain in the order of
10 4 different proteins, and each animal species
contains an even greater number due to differences between the tissues of an individual and
between the individuals themselves; furthermore, the protein spectrum changes during the
course of development. The number of different
proteins to be found in extant organisms may be
as high as 10 12 • The description of this variety, its
origin and biological significance is the most
extensive theme in comparative biochemistry.
This chapter will concern itself with the possibilities for structural variation and the general metabolism of proteins; further chapters will deal with
comparative studies of individual proteins.
3.1.1 Protein Constituents
The primary products of protein biosynthesis are
linear polymers of the 20 standard amino acids.
There has been much speculation about why the
a-amino acids, out of the many possible aminocarbonic acids, should be used in the construction
of proteins; why only those particular 20; and
why only in the L-configuration. Undoubtedly,
this has to do with the changing relationships
between the evolution of amino acid metabolism
3.3
3.3.1
3.3.2
3.3.3
3.3.4
3.3.5
3.4
3.4.1
3.4.2
3.4.3
Proteolysis
Exopeptidases
Serine Proteinases
Cysteine Proteinases
Aspartate Proteinases
Metalloproteinases
Proteinase Inhibitors
Serine-Proteinase Inhibitors
Cysteine-Proteinase Inhibitors
az-Macroglobulins
References
and that of the genetic code, about which there is
as yet no general agreement [245]. The analysis of
amino acid composition is part of the routine
work of the protein chemist, and innumerable
tables of data are now available. Despite the considerable differences between individual proteins,
the spectrum of the protein-bound amino acids
varies much less than that of the free amino acids
(Table 3.1). The number of codons in the genetic
code for individual amino acids varies between
one and six. If each of the 61 amino acid codons
occurred at the same frequency, then each amino
acid would be present in the total protein in proportion to the number of its codons. In actual
fact, lysine, aspartic acid and glutamic acid in particular occur more frequently than would be
expected; arginine, on the other hand, is markedly under-represented. This may be because
arginine appeared as a protein constituent quite
late in evolution (the "intruder hypothesis" of
Jukes), or because a previously larger arginine
fraction has, for some reason, been selected
against in the course of evolution (the "selection
hypothesis" of Wallis), e.g. because the peptide
bonds involving arginine are preferred sites for
protease attack, or the extremely basic property
of arginine, in contrast to lysine, cannot be later
modified by substitution. Although the basic
amino acids arginine and lysine together have
eight co dons and the acidic amino acids aspartic
acid and glutamic acid have only four, they are