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

374 Chapter 7: Control of Gene Expression
major groove
major groove
H
N
N
N
G
H
H
O H N
N H N
N H O
C
N
H
H
N
N
A
H
N H O
N H N
N
H O
T
N
CH 3
H
H
minor groove
minor groove
major groove
major groove
H
H
N
H
O
N
H
CH 3
O
H
H
N
N
H
H
N
C
N
O
H
H
N
N
G
N
N
H
N
T
N H N
O H
A
N
N
H
minor groove
minor groove
this structure. When first discovered in the 1960s, it was thought that these proteins
might require direct access to the interior of the double helix to distinguish
between one DNA sequence and another. It is now clear, however, that the outside
of the double helix is studded with DNA sequence information that transcription
regulators recognize: the edge of each base pair presents a distinctive pattern of
hydrogen-bond donors, hydrogen-bond acceptors, and hydrophobic patches
in both the major and minor grooves (Figure 7–7). Because the major groove is
wider and displays more molecular features than does the minor groove, nearly
all transcription regulators make the majority of their contacts with the major
MBoC6 m7.07/7.07
groove—as we shall see.
Transcription Regulators Contain Structural Motifs That Can Read
DNA Sequences
Molecular recognition in biology generally relies on an exact fit between the surfaces
of two molecules, and the study of transcription regulators has provided
some of the clearest examples of this principle. A transcription regulator recognizes
a specific cis-regulatory sequence because the surface of the protein is
extensively complementary to the special surface features of the double helix that
displays that sequence. Each transcription regulator makes a series of contacts
with the DNA, involving hydrogen bonds, ionic bonds, and hydrophobic interactions.
Although each individual contact is weak, the 20 or so contacts that are typically
formed at the protein–DNA interface add together to ensure that the interaction
is both highly specific and very strong (Figure 7–8). In fact, DNA–protein
Figure 7–7 How the different base
pairs in DNA can be recognized from
their edges without the need to open
the double helix. The four possible
configurations of base pairs are shown,
with potential hydrogen-bond donors
indicated in blue, potential hydrogen-bond
acceptors in red, and hydrogen bonds of
the base pairs themselves as a series of
short, parallel red lines. Methyl groups,
which form hydrophobic protuberances,
are shown in yellow, and hydrogen atoms
that are attached to carbons, and are
therefore unavailable for hydrogen-bonding,
are white. From the major groove, each of
the four base-pair configurations projects
a unique pattern of features. (From
C. Branden and J. Tooze, Introduction
to Protein Structure, 2nd ed. New York:
Garland Publishing, 1999.)