Essential Cell Biology 5th edition

154 CHAPTER 4 Protein Structure and Function
The set of covalent modifications that a protein contains at any moment
constitutes an important form of regulation. The attachment or removal
of these modifying groups can change a protein’s activity or stability, its
binding partners, or its location inside the cell. Covalent modifications
thus enable the cell to make optimal use of the proteins it produces, and
they allow the cell to respond rapidly to changes in its environment.
QUESTION 4–7
Either protein phosphorylation or
the binding of a nucleotide (such as
ATP or GTP) can be used to regulate
a protein’s activity. What do you
suppose are the advantages of each
form of regulation?
Regulatory GTP-Binding Proteins Are Switched On and
Off by the Gain and Loss of a Phosphate Group
Eukaryotic cells have a second way to regulate protein activity by phosphate
addition and removal. In this case, however, the phosphate is not
enzymatically transferred from ATP to the protein. Instead, the phosphate
is part of a guanine nucleotide—guanosine triphosphate (GTP)—that
binds tightly various types of GTP-binding proteins. These proteins act
as molecular switches: they are in their active conformation when GTP is
bound, but they can hydrolyze this GTP to GDP—which releases a phosphate
and flips the protein to an inactive conformation (Movie 4.10). As
with protein phosphorylation, this process is reversible: the active conformation
is regained by dissociation of the GDP, followed by the binding
of a fresh molecule of GTP (Figure 4−48).
Hundreds of GTP-binding proteins function as molecular switches in
cells. The dissociation of GDP and its replacement by GTP, which turns the
switch on, is often stimulated in response to cell signals. The GTP-binding
proteins activated in this way in turn bind to other proteins to regulate
their activities. The crucial role GTP-binding proteins play in intracellular
signaling pathways is discussed in detail in Chapter 16.
ATP Hydrolysis Allows Motor Proteins to Produce
Directed Movements in Cells
We have seen how conformational changes in proteins play a central
part in enzyme regulation and cell signaling. But conformational changes
also play another important role in the operation of the eukaryotic cell:
they enable certain specialized proteins to drive directed movements of
cells and their components. These motor proteins generate the forces
responsible for muscle contraction and most other eukaryotic cell movements.
They also power the intracellular movements of organelles and
macromolecules. For example, they help move chromosomes to opposite
ends of the cell during mitosis (discussed in Chapter 18), and they move
organelles along cytoskeletal tracks (discussed in Chapter 17).
Figure 4−48 Many different GTP-binding
proteins function as molecular switches.
A GTP-binding protein requires the
presence of a tightly bound GTP molecule
to be active. The active protein can shut
itself off by hydrolyzing its bound GTP
to GDP and inorganic phosphate (P i ),
which converts the protein to an inactive
conformation. To reactivate the protein,
the tightly bound GDP must dissociate. As
explained in Chapter 16, this dissociation is
a slow step that can be greatly accelerated
by important regulatory proteins called
guanine nucleotide exchange factors
(GEFs). As indicated, once the GDP
dissociates, a molecule of GTP quickly
replaces it, returning the protein to its
active conformation.
ON
ACTIVE
FAST
GTP-binding protein
GTP
GTP
GTP
BINDING
P
GTP
HYDROLYSIS
OFF
INACTIVE
GDP
GDP
DISSOCIATION
GDP
OFF
INACTIVE
SLOW