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PMID: 8265659 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The SRY high-mobility-group box recognizes DNA by partial intercalation in the minor groove: a topological mechanism of sequence specificity.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 24 ·1993-12-15 ·Pages 11990-4

King CY, Weiss MA

Abstract

SRY, a putative transcription factor encoded by the sex-determining region of the human Y chromosome, regulates a genetic switch in male development. Impairment of this switch leads to intersex abnormalities of the newborn and is observed in association with mutations in the SRY DNA-binding domain [the high-mobility-group (HMG) box]. Here we show that the SRY HMG box exhibits a novel mechanism of DNA recognition: partial intercalation of a nonpolar side chain in the DNA minor groove. Base stacking (but not base pairing) is interrupted at the site of insertion. Sequence specificity reflects topological requirements of partial intercalation rather than direct readout of base-specific functional groups. Our results predict that the SRY HMG box inserts an alpha-helix into a widened minor groove at the center of a sharp DNA bend. A similar mechanism may underlie binding of SRY and homologous HMG proteins to four-way junctions (Holliday intermediates) and other noncanonical DNA structures.

MeSH Terms
Base Composition Base Sequence DNA/chemistry,metabolism DNA-Binding Proteins/genetics,metabolism Humans Magnetic Resonance Spectroscopy Male Models, Molecular Molecular Sequence Data Nuclear Proteins Nucleic Acid Conformation Promoter Regions, Genetic Sex-Determining Region Y Protein Substrate Specificity Transcription Factors/metabolism Y Chromosome
Chemicals
DNA-Binding Proteins Nuclear Proteins SRY protein, human Sex-Determining Region Y Protein Transcription Factors DNA
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
King C Y
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Weiss M A
References (33)
33 references, click to expand
  1. Steroid diamine-nucleic acid interactions: partial insertion of dipyrandium between unstacked base pairs of the poly(dA-dT) duplex in solution.
    Proc Natl Acad Sci U S A. 1979 Jan;76(1):24-8 PMID: 284337
  2. Co-crystal structure of TBP recognizing the minor groove of a TATA element.
    Nature. 1993 Oct 7;365(6446):520-7 PMID: 8413605
  3. Gene regulation by proteins acting nearby and at a distance.
    Nature. 1986 Aug 21-27;322(6081):697-701 PMID: 3018583
  4. Crystal structure of trp repressor/operator complex at atomic resolution.
    Nature. 1988 Sep 22;335(6188):321-9 PMID: 3419502
  5. Pyrimidine.pyrimidine base-pair mismatches in DNA. A nuclear magnetic resonance study of T.T pairing at neutral pH and C.C pairing at acidic pH in dodecanucleotide duplexes.
    J Mol Biol. 1988 Jul 5;202(1):139-55 PMID: 2845094
  6. H NMR study of a complex between the lac repressor headpiece and a 22 base pair symmetric lac operator.
    Biochemistry. 1989 Apr 4;28(7):2985-91 PMID: 2742823
  7. Molecular mechanisms governing species-specific transcription of ribosomal RNA.
    Cell. 1989 Nov 3;59(3):489-97 PMID: 2805069
  8. Parameters for the calculation of proton NMR chemical shifts of oligoribonucleotides.
    J Biomol Struct Dyn. 1985 Feb;2(4):693-707 PMID: 2856017
  9. Flexible recognition of rapidly evolving promoter sequences by mitochondrial transcription factor 1.
    Genes Dev. 1989 Dec;3(12B):2202-17 PMID: 2628167
  10. Structural studies of protein-nucleic acid interaction: the sources of sequence-specific binding.
    Q Rev Biophys. 1990 Aug;23(3):205-80 PMID: 2204954
  11. Protein--DNA contacts in the structure of a homeodomain--DNA complex determined by nuclear magnetic resonance spectroscopy in solution.
    EMBO J. 1990 Oct;9(10):3085-92 PMID: 1976507
  12. Expression of a candidate sex-determining gene during mouse testis differentiation.
    Nature. 1990 Nov 29;348(6300):450-2 PMID: 2247150
  13. The DNA sequence at echinomycin binding sites determines the structural changes induced by drug binding: NMR studies of echinomycin binding to [d(ACGTACGT)]2 and [d(TCGATCGA)]2.
    Biochemistry. 1991 Mar 5;30(9):2483-94 PMID: 2001374
  14. Solution structure of the luzopeptin-DNA complex.
    Biochemistry. 1991 Apr 23;30(16):4026-41 PMID: 1850297
  15. Fos-Jun heterodimers and Jun homodimers bend DNA in opposite orientations: implications for transcription factor cooperativity.
    Cell. 1991 Jul 26;66(2):317-26 PMID: 1906785
  16. DNA-binding properties of the product of the testis-determining gene and a related protein.
    Nature. 1991 Nov 28;354(6351):317-20 PMID: 1956382
  17. DNA-binding properties of the HMG domain of the lymphoid-specific transcriptional regulator LEF-1.
    Genes Dev. 1991 Dec;5(12B):2567-78 PMID: 1752444
  18. TFIID binds in the minor groove of the TATA box.
    Cell. 1991 Dec 20;67(6):1231-40 PMID: 1760847
  19. DNA binding activity of recombinant SRY from normal males and XY females.
    Science. 1992 Jan 24;255(5043):453-6 PMID: 1734522
  20. Yeast and human TFIID with altered DNA-binding specificity for TATA elements.
    Cell. 1992 Feb 21;68(4):721-30 PMID: 1739977
  21. Specific binding of chromosomal protein HMG1 to DNA damaged by the anticancer drug cisplatin.
    Science. 1992 Apr 10;256(5054):234-7 PMID: 1566071
  22. DNA--protein interactions. HMG has DNA wrapped up.
    Nature. 1992 May 28;357(6376):282-3 PMID: 1589033
  23. Sequence-specific interaction of the HMG box proteins TCF-1 and SRY occurs within the minor groove of a Watson-Crick double helix.
    EMBO J. 1992 Aug;11(8):3039-44 PMID: 1639073
  24. Transcription factors: structural families and principles of DNA recognition.
    Annu Rev Biochem. 1992;61:1053-95 PMID: 1497306
  25. SRY, like HMG1, recognizes sharp angles in DNA.
    EMBO J. 1992 Dec;11(12):4497-506 PMID: 1425584
  26. Crystal structure of TFIID TATA-box binding protein.
    Nature. 1992 Nov 5;360(6399):40-6 PMID: 1436073
  27. SRY recognizes conserved DNA sites in sex-specific promoters.
    Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):1097-101 PMID: 8430080
  28. Structure of the HMG box motif in the B-domain of HMG1.
    EMBO J. 1993 Apr;12(4):1311-9 PMID: 8467791
  29. Pathology of 46,XY pure gonadal dysgenesis: absence of testis differentiation associated with mutations in the testis-determining factor.
    Differentiation. 1993 Jan;52(2):151-9 PMID: 8472885
  30. Ancestry and diversity of the HMG box superfamily.
    Nucleic Acids Res. 1993 May 25;21(10):2493-501 PMID: 8506143
  31. The structure of the four-way junction in DNA.
    Annu Rev Biophys Biomol Struct. 1993;22:299-328 PMID: 8347993
  32. Crystal structure of a yeast TBP/TATA-box complex.
    Nature. 1993 Oct 7;365(6446):512-20 PMID: 8413604
  33. Structure of a B-DNA dodecamer. II. Influence of base sequence on helix structure.
    J Mol Biol. 1981 Jul 15;149(4):761-86 PMID: 6273591
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.90.24.11990
Published
1993-12-15
Pages
11990-4
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC48111
Subset
IM
Grants
NICHD NIH HHS · HD26465 · United States
External Links
PubMed source DOI: 10.1073/pnas.90.24.11990 PMC Full Text View journal details
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