The overall goal of the proposed work is to provide a quantitative biophysical description of the protein folding and binding kinetics and thermodynamics of members of the kB family as they interact with members of the NFKB family. Integration with the Wolynes project will correlate theory and experiment to develop a deeper understanding of how the protein structure determines its biophysical properties. Integration with the Dyson project will cross the time-scale boundaries from NMR time scale dynamics to longer time scales probed by H/D exchange and smFRET. Integration with the Hoffmann and Ghosh projects will provide a link between biophysical properties and function. A focus of the project is the intrinsic disorder of iKBa AR5-AR6-C-terminal EST-containing region and its role in establishing functional control of NFKB signaling.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM071862-07
Application #
8459437
Study Section
Special Emphasis Panel (ZRG1-BCMB-D)
Project Start
Project End
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
7
Fiscal Year
2013
Total Cost
$351,701
Indirect Cost
$113,022
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Wolynes, Peter G (2015) Evolution, energy landscapes and the paradoxes of protein folding. Biochimie 119:218-30
Potoyan, Davit A; Wolynes, Peter G (2014) On the dephasing of genetic oscillators. Proc Natl Acad Sci U S A 111:2391-6
Alverdi, Vera; Hetrick, Byron; Joseph, Simpson et al. (2014) Direct observation of a transient ternary complex during I?B?-mediated dissociation of NF-?B from DNA. Proc Natl Acad Sci U S A 111:225-30
Tao, Zhihua; Fusco, Amanda; Huang, De-Bin et al. (2014) p100/I?B? sequesters and inhibits NF-?B through kappaBsome formation. Proc Natl Acad Sci U S A 111:15946-51
Schafer, N P; Kim, B L; Zheng, W et al. (2014) Learning To Fold Proteins Using Energy Landscape Theory. Isr J Chem 54:1311-1337
Dembinski, Holly; Wismer, Kevin; Balasubramaniam, Deepa et al. (2014) Predicted disorder-to-order transition mutations in I?B? disrupt function. Phys Chem Chem Phys 16:6480-5
Alves, Bryce N; Tsui, Rachel; Almaden, Jonathan et al. (2014) I?B? is a key regulator of B cell expansion by providing negative feedback on cRel and RelA in a stimulus-specific manner. J Immunol 192:3121-32
Ferreiro, Diego U; Komives, Elizabeth A; Wolynes, Peter G (2014) Frustration in biomolecules. Q Rev Biophys 47:285-363
Kim, Bobby L; Schafer, Nicholas P; Wolynes, Peter G (2014) Predictive energy landscapes for folding ?-helical transmembrane proteins. Proc Natl Acad Sci U S A 111:11031-6
Cervantes, Carla F; Handley, Lindsey D; Sue, Shih-Che et al. (2013) Long-range effects and functional consequences of stabilizing mutations in the ankyrin repeat domain of IýýBýý. J Mol Biol 425:902-13

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