Abstract

Tools of structural and computational biology will be used to uncover principles of biological recognition and assembly at the root of normal and pathological molecular complexes. The nature of the amyloid state of proteins, found in Alzheimer's and other neurodegenerative diseases, will be explored by x-ray diffraction and related methods. The primary goals will be learn the 3D structure of amyloid, which from preliminary experiments seems to be a dehydrated, hydrogen-bonded state. A second goal will be to understand the possible relationship of amyloid to the phenomenon of 3D domain swapping, found in other protein aggregates. In another line of work, computational methods will be extended for identifying the interacting networks of macromolecules in cells. Data from fully sequenced genomes will be basis of this work. Also structures of proteins will be determined that display interactions related to the general questions of recognition and assembly. One of these is glutamine synthetase, which may serve as an excellent target for a drug against tuberculosis.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
2P01GM031299-19
Application #
6448186
Study Section
Project Start
1983-04-01
Project End
2006-04-30
Budget Start
Budget End
Support Year
19
Fiscal Year
2001
Total Cost
$158,272
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Type
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Katsir, Galit; Jarvis, Michael; Phillips, Martin et al. (2015) The Escherichia coli NarL receiver domain regulates transcription through promoter specific functions. BMC Microbiol 15:174
Laganowsky, Arthur; Zhao, Minglei; Soriaga, Angela B et al. (2011) An approach to crystallizing proteins by metal-mediated synthetic symmetrization. Protein Sci 20:1876-90
Yeates, Todd O; Crowley, Christopher S; Tanaka, Shiho (2010) Bacterial microcompartment organelles: protein shell structure and evolution. Annu Rev Biophys 39:185-205
Boutz, Daniel R; Cascio, Duilio; Whitelegge, Julian et al. (2007) Discovery of a thermophilic protein complex stabilized by topologically interlinked chains. J Mol Biol 368:1332-44
Banatao, D Rey; Cascio, Duilio; Crowley, Christopher S et al. (2006) An approach to crystallizing proteins by synthetic symmetrization. Proc Natl Acad Sci U S A 103:16230-5
Norcross, Todd S; Yeates, Todd O (2006) A framework for describing topological frustration in models of protein folding. J Mol Biol 362:605-21
Nelson, Rebecca; Eisenberg, David (2006) Recent atomic models of amyloid fibril structure. Curr Opin Struct Biol 16:260-5
Laidman, Janel; Forse, G Jason; Yeates, Todd O (2006) Conformational change and assembly through edge beta strands in transthyretin and other amyloid proteins. Acc Chem Res 39:576-83
Beeby, Morgan; O'Connor, Brian D; Ryttersgaard, Carsten et al. (2005) The genomics of disulfide bonding and protein stabilization in thermophiles. PLoS Biol 3:e309
Schmidt, Amy E; Chand, Hitendra S; Cascio, Dulio et al. (2005) Crystal structure of Kunitz domain 1 (KD1) of tissue factor pathway inhibitor-2 in complex with trypsin. Implications for KD1 specificity of inhibition. J Biol Chem 280:27832-8

Showing the most recent 10 out of 127 publications