A Peptide Motif That Recognizes A.T Tracts in DNA

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1993 Dec 1

PMID 8248247

Citations 11

Authors

B J Reardon

R S Winters

D Gordon

E Winter

Affiliations

Soon will be listed here.

Abstract

The DAT1 gene of Saccharomyces cerevisiae encodes a DNA binding protein that specifically interacts with nonalternating oligo(A).oligo(T) tracts (A.T tracts). Deletion analysis of DAT1 coding information showed that the amino-terminal 36 residues are sufficient for specific DNA binding activity. Furthermore, a 35-residue synthetic peptide corresponding to amino acids 2-36 bound to A.T tracts with an equilibrium dissociation constant of 4 x 10(-10) M. Within this region the pentad Gly-Arg-Lys-Pro-Gly is repeated three times. Mutational analysis revealed that the Arg side chains are required for high-affinity binding, whereas the other pentad side chains are dispensable. Chemical interference experiments showed that the DAT1 protein interacts with the minor groove of the double helix. The data suggest that the pentad arginines interact in a cooperative manner with a repeated minor groove feature of A.T tract DNA to achieve high-affinity recognition. Amino acid similarities with other DNA binding proteins suggest that the DAT1 protein pentad represents a specialized example of a widespread motif used by proteins to recognize A.T base pairs.

Citing Articles

Genomic instability causes HGF gene activation in colon cancer cells, promoting their resistance to necroptosis.

Seneviratne D, Ma J, Tan X, Kwon Y, Muhammad E, Melhem M Gastroenterology. 2014; 148(1):181-191.e17.

PMID: 25244939 PMC: 4274190. DOI: 10.1053/j.gastro.2014.09.019.

Somatic mutation and functional polymorphism of a novel regulatory element in the HGF gene promoter causes its aberrant expression in human breast cancer.

Ma J, DeFrances M, Zou C, Johnson C, Ferrell R, Zarnegar R J Clin Invest. 2009; 119(3):478-91.

PMID: 19188684 PMC: 2648687. DOI: 10.1172/JCI36640.

Computational reconstruction of transcriptional regulatory modules of the yeast cell cycle.

Wu W, Li W, Chen B BMC Bioinformatics. 2006; 7:421.

PMID: 17010188 PMC: 1637117. DOI: 10.1186/1471-2105-7-421.

AHM1, a novel type of nuclear matrix-localized, MAR binding protein with a single AT hook and a J domain-homologous region.

Morisawa G, Moda I, Tamai A, Iwabuchi M, Meshi T Plant Cell. 2000; 12(10):1903-16.

PMID: 11041885 PMC: 149128. DOI: 10.1105/tpc.12.10.1903.

The C-terminal DNA-binding domain of Chironomus BR gene products shows preferential affinity for (dA.dT)-rich sequences.

Botella L, Nieto A Mol Gen Genet. 1996; 251(4):422-7.

PMID: 8709945 DOI: 10.1007/BF02172370.

References

Lue N, Buchman A, Kornberg R . Activation of yeast RNA polymerase II transcription by a thymidine-rich upstream element in vitro. Proc Natl Acad Sci U S A. 1989; 86(2):486-90. PMC: 286495. DOI: 10.1073/pnas.86.2.486. View

Coll M, Frederick C, Wang A, Rich A . A bifurcated hydrogen-bonded conformation in the d(A.T) base pairs of the DNA dodecamer d(CGCAAATTTGCG) and its complex with distamycin. Proc Natl Acad Sci U S A. 1987; 84(23):8385-9. PMC: 299547. DOI: 10.1073/pnas.84.23.8385. View

Seeman N, Rosenberg J, Rich A . Sequence-specific recognition of double helical nucleic acids by proteins. Proc Natl Acad Sci U S A. 1976; 73(3):804-8. PMC: 336007. DOI: 10.1073/pnas.73.3.804. View

Ashley C, Pendleton C, Jennings W, Saxena A, Glover C . Isolation and sequencing of cDNA clones encoding Drosophila chromosomal protein D1. A repeating motif in proteins which recognize at DNA. J Biol Chem. 1989; 264(14):8394-401. View

NELSON H, Finch J, Luisi B, Klug A . The structure of an oligo(dA).oligo(dT) tract and its biological implications. Nature. 1987; 330(6145):221-6. DOI: 10.1038/330221a0. View

Weir H, Kraulis P, Hill C, Raine A, Laue E, Thomas J . Structure of the HMG box motif in the B-domain of HMG1. EMBO J. 1993; 12(4):1311-9. PMC: 413342. DOI: 10.1002/j.1460-2075.1993.tb05776.x. View

Struhl K . Naturally occurring poly(dA-dT) sequences are upstream promoter elements for constitutive transcription in yeast. Proc Natl Acad Sci U S A. 1985; 82(24):8419-23. PMC: 390927. DOI: 10.1073/pnas.82.24.8419. View

Otting G, Qian Y, Billeter M, Muller M, Affolter M, Gehring W . Protein--DNA contacts in the structure of a homeodomain--DNA complex determined by nuclear magnetic resonance spectroscopy in solution. EMBO J. 1990; 9(10):3085-92. PMC: 552035. DOI: 10.1002/j.1460-2075.1990.tb07505.x. View

Levinger L, Varshavsky A . Protein D1 preferentially binds A + T-rich DNA in vitro and is a component of Drosophila melanogaster nucleosomes containing A + T-rich satellite DNA. Proc Natl Acad Sci U S A. 1982; 79(23):7152-6. PMC: 347296. DOI: 10.1073/pnas.79.23.7152. View

10.

Sturm R, Baumruker T, Franza Jr B, Herr W . A 100-kD HeLa cell octamer binding protein (OBP100) interacts differently with two separate octamer-related sequences within the SV40 enhancer. Genes Dev. 1987; 1(10):1147-60. DOI: 10.1101/gad.1.10.1147. View

11.

Kissinger C, Liu B, Kornberg T, Pabo C . Crystal structure of an engrailed homeodomain-DNA complex at 2.8 A resolution: a framework for understanding homeodomain-DNA interactions. Cell. 1990; 63(3):579-90. DOI: 10.1016/0092-8674(90)90453-l. View

12.

Reeves R, Nissen M . The A.T-DNA-binding domain of mammalian high mobility group I chromosomal proteins. A novel peptide motif for recognizing DNA structure. J Biol Chem. 1990; 265(15):8573-82. View

13.

Ballard M, Tyndall W, Shingle J, Hall D, Winter E . Tyrosine phosphorylation of a yeast 40 kDa protein occurs in response to mating pheromone. EMBO J. 1991; 10(12):3753-8. PMC: 453111. DOI: 10.1002/j.1460-2075.1991.tb04944.x. View

14.

Solomon M, Strauss F, Varshavsky A . A mammalian high mobility group protein recognizes any stretch of six A.T base pairs in duplex DNA. Proc Natl Acad Sci U S A. 1986; 83(5):1276-80. PMC: 323058. DOI: 10.1073/pnas.83.5.1276. View

15.

Churchill M, Travers A . Protein motifs that recognize structural features of DNA. Trends Biochem Sci. 1991; 16(3):92-7. DOI: 10.1016/0968-0004(91)90040-3. View

16.

Ner S . HMGs everywhere. Curr Biol. 1992; 2(4):208-10. DOI: 10.1016/0960-9822(92)90541-h. View

17.

Karlin S, Blaisdell B, Sapolsky R, Cardon L, Burge C . Assessments of DNA inhomogeneities in yeast chromosome III. Nucleic Acids Res. 1993; 21(3):703-11. PMC: 309172. DOI: 10.1093/nar/21.3.703. View

18.

Laughon A . DNA binding specificity of homeodomains. Biochemistry. 1991; 30(48):11357-67. DOI: 10.1021/bi00112a001. View

19.

Chen W, Tabor S, Struhl K . Distinguishing between mechanisms of eukaryotic transcriptional activation with bacteriophage T7 RNA polymerase. Cell. 1987; 50(7):1047-55. DOI: 10.1016/0092-8674(87)90171-1. View

20.

Sluka J, Horvath S, Glasgow A, Simon M, Dervan P . Importance of minor-groove contacts for recognition of DNA by the binding domain of Hin recombinase. Biochemistry. 1990; 29(28):6551-61. DOI: 10.1021/bi00480a002. View