Abstract

This proposal focuses on the structure and stability of the leucine zipper, a recently discovered sequence motif that mediates dimerization of a large family of eukaryotic transcription factors. The long term objectives of the proposed research are to understand the energetic and structural basis for the stability and specificity of leucine zipper dimerization. The proposed experiments will provide significant insights into protein-protein interactions, protein stability, structure-function relationships in coiled coil proteins, transcriptional regulations, oncogenesis and molecular recognition.
The specific aims of the research are: (1) To complete the high resolution crystallographic refinement of the x-ray crystal structure of a synthetic peptide corresponding to the leucine zipper of the yeast transcriptional activator GCN4. (2) To crystallize the leucine zipper sequences of the nuclear oncogene products Fos and Jun. (3) To quantify the stabilizing contributions of individual interactions in the GCN4 leucine zipper using structural and thermodynamic studies of peptide variants.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM048958-02
Application #
3308349
Study Section
Molecular and Cellular Biophysics Study Section (BBCA)
Project Start
1992-06-01
Project End
1996-05-31
Budget Start
1993-06-01
Budget End
1994-05-31
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
University of California Berkeley
Department
Type
Schools of Arts and Sciences
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704

  Publications

Tosha, Takehiko; Behera, Rabindra K; Ng, Ho-Leung et al. (2012) Ferritin protein nanocage ion channels: gating by N-terminal extensions. J Biol Chem 287:13016-25
Fraser, James S; van den Bedem, Henry; Samelson, Avi J et al. (2011) Accessing protein conformational ensembles using room-temperature X-ray crystallography. Proc Natl Acad Sci U S A 108:16247-52
Tosha, Takehiko; Ng, Ho-Leung; Bhattasali, Onita et al. (2010) Moving metal ions through ferritin-protein nanocages from three-fold pores to catalytic sites. J Am Chem Soc 132:14562-9
Fraser, James S; Clarkson, Michael W; Degnan, Sheena C et al. (2009) Hidden alternative structures of proline isomerase essential for catalysis. Nature 462:669-73
Lin, Michael Z; McKeown, Michael R; Ng, Ho-Leung et al. (2009) Autofluorescent proteins with excitation in the optical window for intravital imaging in mammals. Chem Biol 16:1169-79
Barth, Patrick; Schoeffler, Allyn; Alber, Tom (2008) Targeting metastable coiled-coil domains by computational design. J Am Chem Soc 130:12038-44
Bertin, Aurelie; McMurray, Michael A; Grob, Patricia et al. (2008) Saccharomyces cerevisiae septins: supramolecular organization of heterooligomers and the mechanism of filament assembly. Proc Natl Acad Sci U S A 105:8274-9
Sales, Mark; Plecs, Joseph J; Holton, James M et al. (2007) Structure of a designed, right-handed coiled-coil tetramer containing all biological amino acids. Protein Sci 16:2224-32
Cellitti, Jason; Llinas, Manuel; Echols, Nathaniel et al. (2007) Exploring subdomain cooperativity in T4 lysozyme I: structural and energetic studies of a circular permutant and protein fragment. Protein Sci 16:842-51
Barth, P; Alber, T; Harbury, P B (2007) Accurate, conformation-dependent predictions of solvent effects on protein ionization constants. Proc Natl Acad Sci U S A 104:4898-903

Showing the most recent 10 out of 22 publications