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

PROTEIN FUNCTION
165
unstructured
region
rapid
collisions
structured
domain
scaffold protein
reacting
proteins
scaffold ready
for reuse
Discs-large protein (Dlg), a protein of about 900 amino acids that is concentrated
in special regions beneath the plasma membrane in epithelial cells and at synapses.
Dlg contains binding sites for at least seven other proteins, interspersed
with regions of more flexible polypeptide chain. An ancient protein, conserved in
organisms as diverse as sponges, worms, flies, and humans, Dlg derives its name
from the mutant phenotype of the organism in which it was first discovered; the
cells in the imaginal discs of a Drosophila embryo with a mutation in the Dlg gene
fail to stop proliferating when they should, and they produce unusually large discs
whose epithelial cells can form tumors.
Although incompletely studied, MBoC6 Dlg m3.80c/3.71 and a large number of similar scaffold
proteins are thought to function like the protein that is schematically illustrated in
Figure 3–78. By binding a specific set of interacting proteins, these scaffolds can
enhance the rate of critical reactions, while also confining them to the particular
region of the cell that contains the scaffold. For similar reasons, cells also make
extensive use of scaffold RNA molecules, as discussed in Chapter 7.
+
product
Figure 3–78 How the proximity created
by scaffold proteins can greatly speed
reactions in a cell. In this example, long
unstructured regions of polypeptide chain
in a large scaffold protein connect a series
of structured domains that bind a set of
reacting proteins. The unstructured regions
serve as flexible “tethers” that greatly speed
reaction rates by causing a rapid, random
collision of all of the proteins that are bound
to the scaffold. (For specific examples of
protein tethering, see Figure 3–54 and
Figure 16–18; for scaffold RNA molecules,
see Figure 7–49B.)
Many Proteins Are Controlled by Covalent Modifications That
Direct Them to Specific Sites Inside the Cell
We have thus far described only a few ways in which proteins are post-translationally
modified. A large number of other such modifications also occur, more than
200 distinct types being known. To give a sense of the variety, Table 3–3 presents
Table 3–3 Some Molecules Covalently Attached to Proteins Regulate Protein
Function
Modifying group
Phosphate on Ser, Thr,
or Tyr
Methyl on Lys
Acetyl on Lys
Palmityl group on Cys
N-acetylglucosamine on
Ser or Thr
Ubiquitin on Lys
Some prominent functions
Drives the assembly of a protein into larger complexes
(see Figure 15–11)
Helps to create distinct regions in chromatin through
forming either mono-, di-, or trimethyl lysine in histones
(see Figure 4–36)
Helps to activate genes in chromatin by modifying
histones (see Figure 4–33)
This fatty acid addition drives protein association with
membranes (see Figure 10–18)
Controls enzyme activity and gene expression in glucose
homeostasis
Monoubiquitin addition regulates the transport of
membrane proteins in vesicles (see Figure 13–50)
A polyubiquitin chain targets a protein for degradation
(see Figure 3–70)
Ubiquitin is a 76-amino-acid polypeptide; there are at least 10 other ubiquitin-related proteins in
mammalian cells.