| Literature References | 1. GUNTHER, C.V., NYE, J.A., BRYNER, R.S. AND GRAVES, B.J.
Sequence-specific DNA binding of the proto-oncoprotein ets-1 defines a
transcriptional activator sequence within the long terminal repeat of the
Moloney murine sarcoma virus.
GENES DEV. 4 667-679 (1990).
2. KARIM, F.D., URNESS, L.D., THUMMEL, C.S., KLEMSZ, M.J., MCKERCHER, S.R.,
CELADA, A., VAN BEVEREN, C., MAKI, R.A., GUNTHER, C.V., NYE, J.A. AND
GRAVES, B.J.
The ETS-domain: a new DNA-binding motif that recognizes a purine-rich core
DNA sequence.
GENES DEV. 4 1451-1453 (1990).
3. WASYLYK, B., HAHN, S.L. AND GIOVANE, A.
The Ets family of transcription factors.
EUR.J.BIOCHEM. 211 7-18 (1993).
4. WERNER, M.H., CLORE, G.M., FISHER, C.L., FISHER, R.J., TRINH, L.,
SHILOACH, J. AND GRONENBORN, A.M.
The solution structure of the human ETS1-DNA complex reveals a novel
mode of binding and true side chain intercalation.
CELL 83 761-771 (1995).
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| Documentation | Transcription factors are protein molecules that bind to specific DNA
sequences in the genome, resulting in the induction or inhibition of gene
transcription [1]. The ets oncogene is such a factor, possessing a region
of 85-90 amino acids known as the ETS domain [1,2]. This domain is rich in
positively-charged and aromatic residues, and binds to purine-rich segments
of DNA. The ETS domain has been idenitified in other transcription factors
such as PU.1, human erg, human elf-1, human elk-1, GA binding protein, and
a number of others [1-3].
The solution structure of a specific human ETS1-DNA complex has been solved
by NMR [4]. The protein-DNA interaction reveals a twist on the general
features of helix-turn-helix (HTH)-DNA interactions. Major groove
recognition involves the C-terminal two-thirds of the HTH recognition helix,
while minor groove recognition occurs via intercalation of the side chain of
Trp-28, which extends from the minor to the major groove [4]. This results
in a kink of ~60 degrees and a widening of the minor groove. These
observations establish the ETS family of DNA-binding proteins as a distinct
family of HTH proteins [4].
ETSDOMAIN is a 4-element fingerprint that provides a signature for the
ETS DNA-binding domain. The fingerprint was derived from an initial
alignment of 7 sequences: the motifs were drawn from conserved regions
spanning virtually the full domain length - motif 1 encodes alpha-helix 2;
motif 2 spans beta-strand 2 and helix 4; motif 3 encodes helix 5; and motif
4 spans strands 3 and 4. Two iterations on OWL27.0 were required to reach
convergence, at which point a true set comprising 70 sequences was
identified. Five partial matches were also found, all of which are related
proteins that fail to make significant matches with one or more motifs.
An update on SPTR39.22_17.3f identified a true set of 125 sequences, and
again 5 partial matches.
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