Systematic method for the detection of potential λ Cro-like DNA-binding regions in proteins

doi:10.1016/0022-2836(87)90681-4

Journal of Molecular Biology

Volume 194, Issue 3, 5 April 1987, Pages 557-564

https://doi.org/10.1016/0022-2836(87)90681-4 Get rights and content

Abstract

We have developed and tested a systematic method for the location and statistical evaluation of potential DNA-binding regions of the λ Cro type in protein sequences. Using this approach to examine proteins expected to contain such regions, we have been able to compile a statistically homogeneous master set of 37 λ Cro-like DNA-binding domains. Examination of a protein database revealed other prokaryotic proteins that are similar to this λ Cro-like group. There are also many DNA-binding proteins that are not found to be significantly similar to the λ Cro group, consistent with previous suggestions that different types of protein sequence may be able to achieve a similar mode of binding and that there exist other modes of sequence-specific DNA-binding. A useful feature of the method is that it can be applied without a computer.

References (50)

BackhausH. et al.
Gene
(1984)
BrandA.H. et al.
Cell
(1985)
DunnJ.J. et al.
J. Mol. Biol.
(1981)
FlammE.L. et al.
J. Mol. Biol.
(1985)
FrackmanS. et al.
J. Mol. Biol.
(1985)
GinsbergA.M. et al.
Cell
(1984)
HowardP.K. et al.
Gene
(1985)
NakayamaN. et al.
J. Biol. Chem.
(1984)
NelsonH.C.M. et al.
Cell
(1985)
NewmanB.J. et al.
Cell
(1984)

PooleS.J. et al.

Cell

(1985)

RyderK. et al.

Cell

(1985)

SangerF. et al.

J. Mol. Biol.

(1982)

SilbersteinS. et al.

J. Mol. Biol.

(1975)

StragierP. et al.

J. Mol. Biol.

(1983)

StragierP. et al.

FEBS Letters

(1985)

WhartonR.P. et al.

Cell

(1984)

AndersonJ.E. et al.

Nature (London)

(1985)

BarkerW.C. et al.

ChenH.R. et al.

DNA

(1982)

ChenI.S.Y. et al.

Science

(1985)

DhaeseP. et al.

Nucl. Acids Res.

(1985)

DoolittleR.F.

FeissM. et al.

GreeneJ.R. et al.

Cited by (134)

The many faces of the helix-turn-helix domain: Transcription regulation and beyond
2005, FEMS Microbiology Reviews
The helix-turn-helix (HTH) domain is a common denominator in basal and specific transcription factors from the three super-kingdoms of life. At its core, the domain comprises of an open tri-helical bundle, which typically binds DNA with the 3rd helix. Drawing on the wealth of data that has accumulated over two decades since the discovery of the domain, we present an overview of the natural history of the HTH domain from the viewpoint of structural analysis and comparative genomics. In structural terms, the HTH domains have developed several elaborations on the basic 3-helical core, such as the tetra-helical bundle, the winged-helix and the ribbon-helix–helix type configurations. In functional terms, the HTH domains are present in the most prevalent transcription factors of all prokaryotic genomes and some eukaryotic genomes. They have been recruited to a wide range of functions beyond transcription regulation, which include DNA repair and replication, RNA metabolism and protein–protein interactions in diverse signaling contexts. Beyond their basic role in mediating macromolecular interactions, the HTH domains have also been incorporated into the catalytic domains of diverse enzymes. We discuss the general domain architectural themes that have arisen amongst the HTH domains as a result of their recruitment to these diverse functions. We present a natural classification, higher-order relationships and phyletic pattern analysis of all the major families of HTH domains. This reconstruction suggests that there were at least 6–11 different HTH domains in the last universal common ancestor of all life forms, which covered much of the structural diversity and part of the functional versatility of the extant representatives of this domain. In prokaryotes the total number of HTH domains per genome shows a strong power-equation type scaling with the gene number per genome. However, the HTH domains in two-component signaling pathways show a linear scaling with gene number, in contrast to the non-linear scaling of HTH domains in single-component systems and sigma factors. These observations point to distinct evolutionary forces in the emergence of different signaling systems with HTH transcription factors. The archaea and bacteria share a number of ancient families of specific HTH transcription factors. However, they do not share any orthologous HTH proteins in the basal transcription apparatus. This differential relationship of their basal and specific transcriptional machinery poses an apparent conundrum regarding the origins of their transcription apparatus.
Phylogenetic analysis and confirmation of the endospore-forming nature of Pasteuria penetrans based on the spo0A gene
2003, FEMS Microbiology Letters
Pasteuria penetrans is an obligate parasite of plant parasitic nematodes and has yet to be grown in vitro. We have cloned the pivotal sporulation gene, spo0A, which is the first whole gene yet to come from this organism. Partial spo0A sequences were also obtained from the related bacteria, Pasteuria ramosa and Alicyclobacillus acidocaldarius. Phylogenetic analyses using the spo0A sequence data from this and previous studies confirmed the closeness of the genera Pasteuria and members of the supergenus Bacillus. A segment of the spo0A gene was also used to show that genetic heterogeneity exists within and between populations of P. penetrans. This may explain, partly at least, the variability of P. penetrans as a biological control agent of nematodes.
COMPASS: A tool for comparison of multiple protein alignments with assessment of statistical significance
2003, Journal of Molecular Biology
We present a novel method for the comparison of multiple protein alignments with assessment of statistical significance (COMPASS). The method derives numerical profiles from alignments, constructs optimal local profile–profile alignments and analytically estimates E-values for the detected similarities. The scoring system and E-value calculation are based on a generalization of the PSI-BLAST approach to profile–sequence comparison, which is adapted for the profile–profile case. Tested along with existing methods for profile–sequence (PSI-BLAST) and profile–profile (prof_sim) comparison, COMPASS shows increased abilities for sensitive and selective detection of remote sequence similarities, as well as improved quality of local alignments. The method allows prediction of relationships between protein families in the PFAM database beyond the range of conventional methods. Two predicted relations with high significance are similarities between various Rossmann-type folds and between various helix-turn-helix-containing families. The potential value of COMPASS for structure/function predictions is illustrated by the detection of an intricate homology between the DNA-binding domain of the CTF/NFI family and the MH1 domain of the Smad family.
Genomic position analyses and the transcription machinery
1998, Journal of Molecular Biology
Position analyses have been devised to extract additional transcriptional information from rapidly expanding genomic data bases. The locations of promoter regulatory sites and also the locations of transcription factor DNA-binding domains are analyzed. Strongly preferred positions of activator binding sites occur in both Escherichia coli and eukaryotes, suggesting specific common features of transcription in the two systems. In both systems regulatory proteins are found to have their DNA-binding domains near termini and the data suggest an evolutionary analysis that complements phylogenetic analysis based on sequence alignments. The results indicate that positional information can be an important adjunct to sequence comparisons in analyzing genomic information.
Complementation of divergent mga genes in group A Streptococcus
1996, Gene
The gene (mga4) encoding the positive regulatory protein, Mga4, was cloned and sequenced from an M type 4 strain (AP4) of Streptococcus pyogenes. The deduced amino acid (aa) sequence of this ‘divergent Mga’ shows 88% identity to the prototype Mgal in its N-terminal half, which contains all three of the predicted helix-turn-helix domains. However, one of the predicted receiver domains of Mgal, which is at its C terminus, is not conserved in the Mga4 aa sequence. Nevertheless, a mutation in mgal was found to be complemented for activation of the gene encoding M protein (emm) by mga4 in trans. This suggests that the aa residues of the C-terminal predicted receiver domain are not critical for activation of emm transcription.
Catalytic mechanism and DNA substrate recognition of Escherichia coli MutY protein
1996, Journal of Biological Chemistry
Escherichia coli MutY protein cleaves A/G- or A/7,8-dihydro-8-oxo-guanine (A/GO)-containing DNA on the A-strand by N-glycosylase and apurinic/apyrimidinic endonuclease or lyase activities. In this paper, we show that MutY can be trapped in a stable covalent enzyme-DNA intermediate in the presence of sodium borohydride, a new finding that supports the grouping of MutY in that class of DNA glycosylases that possess concomitant apurinic/apyrimidinic lyase activity. To potentially help determine the substrate recognition site of MutY, mutant proteins were constructed. MutY proteins with a Gly¹¹⁶→ Ala (G116A) or Asp (G116D) mutation had reduced binding affinities for both A/G- and A/GO-containing DNA substrates. The catalytic parameters, however, were differentially affected. While A/G- and A/GO-containing DNA were cleaved by MutY with specificity constants (k_cat/K_m) of 10 and 3.3 min⁻¹μM⁻¹, respectively, MutY(G116D) cleaved these DNAs 2,300- and 9-fold less efficiently. The catalytic activities of MutY(G116A) with A/G- and A/GO-containing DNA were about the same as that of wild-type MutY. Both MutY(G116A) and MutY(G116D) could be trapped in covalent intermediates with A/GO-containing DNA, but with lower efficiencies than the wild-type enzyme in the presence of sodium borohydride. MutY(G116A) also formed a covalent intermediate with A/G-containing DNA, but MutY(G116D) did not. Since Gly¹¹⁶ of MutY lies in a region that is highly conserved among several DNA glycosylases, it is likely this conserved region is in the proximity of the substrate binding and/or catalytic sites.

View all citing articles on Scopus

View full text

Journal of Molecular Biology

Systematic method for the detection of potential λ Cro-like DNA-binding regions in proteins

Abstract

Gene

Cell

J. Mol. Biol.

J. Mol. Biol.

J. Mol. Biol.

Cell

Gene

J. Biol. Chem.

Cell

Cell

Cell

Cell

J. Mol. Biol.

J. Mol. Biol.

J. Mol. Biol.

FEBS Letters

Cell

Nature (London)

DNA

Science

Nucl. Acids Res.