Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

120 Chapter 3: Proteins
(A)
helix 2
(B)
helix 3
helix 1
COOH
NH 2
(C)
H 2N
yeast
G H R F T K E N V R I L E S W F A K N
R T A F S S E O L A R L K R E F N E N
Drosophila
I
-
E N P Y L D T K G L E N L M K N T S L S R I Q
- - R Y L T E R R R Q Q L S S E L G L N E A Q
I
I
K N W V S N R R R K E K T
K I W F Q N K R A K I K K
I
S COOH
Figure 3–13 A comparison of a class of DNA-binding domains, called homeodomains, in a pair of proteins from
two organisms separated by more than a billion years of evolution. (A) A ribbon model of the structure common to
both proteins. (B) A trace of the α-carbon positions. The three-dimensional structures shown were determined by x-ray
crystallography for the yeast α2 protein (green) and the Drosophila engrailed protein (red). (C) A comparison of amino acid
sequences for the region of the proteins shown in (A) and (B). Black dots mark sites with identical amino acids. Orange dots
indicate the position of a three-amino-acid insert in the α2 protein. (Adapted from C. Wolberger et al., Cell 67:517–528, 1991.
With permission from Elsevier.)
protein family has been more highly conserved than has the amino acid sequence.
In many cases, the amino acid sequences have diverged so far that we cannot be
certain of a family relationship between two proteins without determining their
three-dimensional structures. The yeast α2 MBoC6 protein m3.13/3.13
and the Drosophila engrailed
protein, for example, are both gene regulatory proteins in the homeodomain family
(discussed in Chapter 7). Because they are identical in only 17 of their 60 amino
acid residues, their relationship became certain only by comparing their three-dimensional
structures (Figure 3–13). Many similar examples show that two proteins
with more than 25% identity in their amino acid sequences usually share the
same overall structure.
The various members of a large protein family often have distinct functions.
Some of the amino acid changes that make family members different were no
doubt selected in the course of evolution because they resulted in useful changes
in biological activity, giving the individual family members the different functional
properties they have today. But many other amino acid changes are effectively
“neutral,” having neither a beneficial nor a damaging effect on the basic structure
and function of the protein. In addition, since mutation is a random process, there
must also have been many deleterious changes that altered the three-dimensional
structure of these proteins sufficiently to harm them. Such faulty proteins would
have been lost whenever the individual organisms making them were at enough
of a disadvantage to be eliminated by natural selection.
Protein families are readily recognized when the genome of any organism is
sequenced; for example, the determination of the DNA sequence for the entire
human genome has revealed that we contain about 21,000 protein-coding genes.
(Note, however, that as a result of alternative RNA splicing, human cells can produce
much more than 21,000 different proteins, as will be explained in Chapter
6.) Through sequence comparisons, we can assign the products of at least 40% of
our protein-coding genes to known protein structures, belonging to more than
500 different protein families. Most of the proteins in each family have evolved
to perform somewhat different functions, as for the enzymes elastase and chymotrypsin
illustrated previously in Figure 3–12. As explained in Chapter 1 (see
Figure 1–21), these are sometimes called paralogs to distinguish them from the
many corresponding proteins in different organisms (orthologs, such as mouse
and human elastase).