Abstract

Multidimensional NMR methods will be used to investigate the mechanisms of nucleic-acid recognition by two key eukaryotic transcription factors, the Wilms tumor suppressor protein (WT1) and transcription factor IIIA. These both contain ubiquitous zinc finger motifs and bind both DNA and RNA. The solution structure and dynamics of DNA complexes formed by the +KTS (Lys-Thr-Ser) and -KTS isoforms of WT1 will be determined to obtain insights into the molecular basis by which alternate splicing is able to modulate DNA binding and specificity. The solution structure and dynamics of the complex between zinc fingers 4 - 6 of TFIIIA and a 55-nucleotide RNA molecular encompassing the TFIIIA-binding core region of Xenopus 5S RNA will be determined to provide insights into the molecular basis by which the zinc finger motif can recognize both RNA and DNA.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM036643-16
Application #
6385629
Study Section
Special Emphasis Panel (ZRG1-BBCB (03))
Program Officer
Wehrle, Janna P
Project Start
1986-04-01
Project End
2003-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
16
Fiscal Year
2001
Total Cost
$384,566
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Nikolova, Evgenia N; Stanfield, Robyn L; Dyson, H Jane et al. (2018) CH···O Hydrogen Bonds Mediate Highly Specific Recognition of Methylated CpG Sites by the Zinc Finger Protein Kaiso. Biochemistry 57:2109-2120
Park, Sangho; Phukan, Priti Deka; Zeeb, Markus et al. (2017) Structural Basis for Interaction of the Tandem Zinc Finger Domains of Human Muscleblind with Cognate RNA from Human Cardiac Troponin T. Biochemistry 56:4154-4168
Burge, Russell G; Martinez-Yamout, Maria A; Dyson, H Jane et al. (2014) Structural characterization of interactions between the double-stranded RNA-binding zinc finger protein JAZ and nucleic acids. Biochemistry 53:1495-510
Buck-Koehntop, Bethany A; Stanfield, Robyn L; Ekiert, Damian C et al. (2012) Molecular basis for recognition of methylated and specific DNA sequences by the zinc finger protein Kaiso. Proc Natl Acad Sci U S A 109:15229-34
Buck-Koehntop, Bethany A; Martinez-Yamout, Maria A; Dyson, H Jane et al. (2012) Kaiso uses all three zinc fingers and adjacent sequence motifs for high affinity binding to sequence-specific and methyl-CpG DNA targets. FEBS Lett 586:734-9
Lee, Brian M; Buck-Koehntop, Bethany A; Martinez-Yamout, Maria A et al. (2007) Embryonic neural inducing factor churchill is not a DNA-binding zinc finger protein: solution structure reveals a solvent-exposed beta-sheet and zinc binuclear cluster. J Mol Biol 371:1274-89
Stoll, Raphael; Lee, Brian M; Debler, Erik W et al. (2007) Structure of the Wilms tumor suppressor protein zinc finger domain bound to DNA. J Mol Biol 372:1227-45
Kostic, Milka; Matt, Theresia; Martinez-Yamout, Maria A et al. (2006) Solution structure of the Hdm2 C2H2C4 RING, a domain critical for ubiquitination of p53. J Mol Biol 363:433-50
Lee, Brian M; Xu, Jing; Clarkson, Bryan K et al. (2006) Induced fit and ""lock and key"" recognition of 5S RNA by zinc fingers of transcription factor IIIA. J Mol Biol 357:275-91
Moller, Heiko M; Martinez-Yamout, Maria A; Dyson, H Jane et al. (2005) Solution structure of the N-terminal zinc fingers of the Xenopus laevis double-stranded RNA-binding protein ZFa. J Mol Biol 351:718-30

Showing the most recent 10 out of 78 publications