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

376 PANEL 7–1: Common Structural Motifs in Transcription Regulators
HELIX–TURN–HELIX PROTEINS
recognition helix
3.4
nm
tryptophan repressor lambda Cro lambda repressor
fragment
Originally identified in bacterial transcription regulators, this motif has
since been found in many hundreds of DNA-binding proteins from both
eukaryotes and prokaryotes. It is constructed from two α helices (blue
and red) connected by a short extended chain of amino acids, which
constitutes the “turn.” The two helices are held at a fixed angle, primarily
through interactions between the two helices. The more C-terminal helix
(in red) is called the recognition helix because it fits into the major
groove of DNA; its amino acid side chains, which differ from protein to
protein, play an important part in recognizing the specific DNA sequence
to which the protein binds. All of the proteins shown here bind DNA as
dimers in which the two copies of the recognition helix (in red) are
separated by exactly one turn of the DNA helix (3.4 nm); thus both
recognition helices of the dimer can fit into the major groove of DNA.
CAP fragment
LEUCINE ZIPPER PROTEINS
dimerization
interface
DNA
HOMEODOMAIN PROTEINS
recognition helix
DNA
2
2
Ser
Arg
3
C
3 1
N
Asn
1
(A)
(B)
Arg
DNA
Not long after the first transcription regulators were discovered in
bacteria, genetic analyses of the fruit fly Drosophila led to the
characterization of an important class of genes, the homeotic selector
genes, that play a critical part in orchestrating fly development (discussed
in Chapter 21). It was later shown that these genes coded for
transcription regulators that bound DNA through a structural motif
named the homeodomain. Two different views of the same structure are
shown. (A) The homeodomain is folded into three α helices, which are
packed tightly together by hydrophobic interactions. The part containing
helices 2 and 3 closely resembles the helix–turn–helix motif. (B) The
recognition helix (helix 3, red) forms important contacts with the major
groove of DNA. The asparagine (Asn) of helix 3, for example, contacts an
adenine, as shown in Figure 7–8. A flexible arm attached to helix 1 forms
contacts with nucleotide pairs in the minor groove.
The leucine zipper motif is named
because of the way the two α
helices, one from each monomer, are
joined together to form a short
coiled-coil. These proteins bind DNA
as dimers where the two long α
helices are held together by
interactions between hydrophobic
amino acid side chains (often on
leucines) that extend from one side
of each helix. Just beyond the
dimerization interface, the two α
helices separate from each other to
form a Y-shaped structure, which
allows their side chains to contact
the major groove of DNA. The dimer
thus grips the double helix like a
clothespin on a clothesline.