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

166 Chapter 3: Proteins
(A)
N
A SPECTRUM OF COVALENT MODIFICATIONS PRODUCES A REGULATORY PROTEIN CODE
MOLECULAR SIGNALS DIRECT ADDITION OF COVALENT MODIFICATIONS
and/or and/or and/or and/or
PROTEIN X
THE CODE IS READ
C
Figure 3–79 Multisite protein modification
and its effects. (A) A protein that carries
a post-translational addition to more than
one of its amino acid side chains can
be considered to carry a combinatorial
regulatory code. Multisite modifications
are added to (and removed from) a protein
through signaling networks, and the
resulting combinatorial regulatory code on
the protein is read to alter its behavior in
the cell. (B) The pattern of some covalent
modifications to the protein p53.
BIND TO
PROTEINS
Y AND Z
MOVE TO
or
MOVE TO
or PROTEASOME or
NUCLEUS
FOR DEGRADATION
MOVE TO
PLASMA
MEMBRANE
(B)
SOME KNOWN MODIFICATIONS OF PROTEIN p53
N
C
50 amino acids
P
phosphate Ac acetyl U ubiquitin SUMO
a few of the modifying groups with known regulatory roles. As in phosphate
and ubiquitin additions described previously, these groups are added and then
removed from proteins according to the needs of the cell.
A large number of proteins are now known to be modified on more than one
amino acid side chain, with different regulatory events producing a different pattern
of such modifications. A striking example is the protein p53, which plays a
central part in controlling a cell’s response to adverse circumstances (see Figure
17–62). Through one of four different types of molecular additions, this protein
can be modified at 20 different sites. Because an enormous number of different
combinations of these 20 modifications are possible, the protein’s behavior can
in principle be altered in a huge MBoC6 number e4.44/3.72 of ways. Such modifications will often
create a site on the modified protein that binds it to a scaffold protein in a specific
region of the cell, thereby connecting it—via the scaffold—to the other proteins
required for a reaction at that site.
One can view each protein’s set of covalent modifications as a combinatorial
regulatory code. Specific modifying groups are added to or removed from a protein
in response to signals, and the code then alters protein behavior—changing
the activity or stability of the protein, its binding partners, and/or its specific location
within the cell (Figure 3–79). As a result, the cell is able to respond rapidly
and with great versatility to changes in its condition or environment.
A Complex Network of Protein Interactions Underlies Cell Function
There are many challenges facing cell biologists in this information-rich era when
a large number of complete genome sequences are known. One is the need to
dissect and reconstruct each one of the thousands of protein machines that exist
in an organism such as ourselves. To understand these remarkable protein complexes,
each will need to be reconstituted from its purified protein parts, so that
we can study its detailed mode of operation under controlled conditions in a test
tube, free from all other cell components. This alone is a massive task. But we now
know that each of these subcomponents of a cell also interacts with other sets of
macromolecules, creating a large network of protein–protein and protein–nucleic
acid interactions throughout the cell. To understand the cell, therefore, we will
need to analyze most of these other interactions as well.