 |
PDBsum entry 2pij
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transcription
|
PDB id
|
|
|
|
2pij
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Transitive homology-Guided structural studies lead to discovery of cro proteins with 40% sequence identity but different folds.
|
|
|
Authors
|
|
C.G.Roessler,
B.M.Hall,
W.J.Anderson,
W.M.Ingram,
S.A.Roberts,
W.R.Montfort,
M.H.Cordes.
|
|
|
Ref.
|
|
Proc Natl Acad Sci U S A, 2008,
105,
2343-2348.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Proteins that share common ancestry may differ in structure and function because
of divergent evolution of their amino acid sequences. For a typical diverse
protein superfamily, the properties of a few scattered members are known from
experiment. A satisfying picture of functional and structural evolution in
relation to sequence changes, however, may require characterization of a larger,
well chosen subset. Here, we employ a "stepping-stone" method, based on
transitive homology, to target sequences intermediate between two related
proteins with known divergent properties. We apply the approach to the question
of how new protein folds can evolve from preexisting folds and, in particular,
to an evolutionary change in secondary structure and oligomeric state in the Cro
family of bacteriophage transcription factors, initially identified by
sequence-structure comparison of distant homologs from phages P22 and lambda. We
report crystal structures of two Cro proteins, Xfaso 1 and Pfl 6, with sequences
intermediate between those of P22 and lambda. The domains show 40% sequence
identity but differ by switching of alpha-helix to beta-sheet in a C-terminal
region spanning approximately 25 residues. Sedimentation analysis also suggests
a correlation between helix-to-sheet conversion and strengthened dimerization.
|
|
|
|
|
|
|
|
Figure 3.
Comparison of Xfaso 1 and Pfl 6. (A and B) Crystal structures
of Xfaso 1 (A) and Pfl 6 (B) with ribbon diagrams for the
biological dimers shown. The Xfaso 1 asymmetric unit has a third
subunit (data not shown). Cys 42 and Cys 55 are indicated for
one subunit of Xfaso 1 to show spatial proximity in the reduced
form. (C) One possible sequence alignment of Xfaso 1 and Pfl 6,
annotated with secondary structures. This alignment gives 40%
sequence identity across 65 residues, with two gaps. The
unstructured C termini of Xfaso 1 (16 residues) and Pfl 6 (7
residues) are not included in the alignment.
|
|
Figure 4.
Summary of stepping-stone results and working model for Cro
structural evolution. Hypothetical or qualitative aspects are
gray. For example, structures of the common ancestor and Afe01
are known only at the level of general fold either from previous
outgroup analysis (ancestor) or from low-resolution data in the
present study (Afe01). One possible phylogenetic tree topology
is indicated by dashed gray lines. The different colors of the
second subunits shown for Pfl 6 Cro (gold) and λ Cro (red) are
intended to indicate the stronger dimerization of the latter.
(Insets) Residues in the ball-and-socket region of Pfl 6 Cro and
λ Cro.
|
|
|
|
|
|
|
|
|
|
