We plan to continue our investigations into the interactions of polyphosphorylated proteins and metals, using the egg yolk phosphoprotein phosvitin as the prototype of such proteins and emphasizing its interactions with iron in particular. While we hope that these studies will generate biochemically sound and testable working hypotheses regarding the hitherto largely unknown biological function of phosvitins in egg producing vertebrates and their developing egg-embryo systems, we expect also that the results will be relevant to some of the relatively recently discovered mammalian polyphosphoproteins that contain phosvitin-like phosphoserine clusters and are associated with, for example, neural, dermal and dental tissue or cells. In essence, we seek to establish the manner in which iron and other metals are coordinated within the phosphoprotein complex, the extent to which such coordination may be non-uniform within and among given proteins, the effects that metal binding and protein conformation may mutually exert on each other, and the minimal structure required for the maintenance of the static and dynamic 'native' character of these complexes. We hope to accomplish these by a combination of methods that permit comparative and correlated measurements of binding stoichiometries, kinetic parameters of iron release, and characteristic features of diverse optical and magnetic resonance spectra of the complexes. Our experimental material consists of a range of proteins derived from species representing a wide variety of taxa and a significant diversity of molecular size, composition and, presumably, structure. This inventory is and will continue to be augmented by specific fragments derived from these proteins and by specifically modified proteins and fragments such that potential ligand groups are or will be selectively altered or removed. We also wish to pursue past indications that the iron-phosvitin interaction may induce covalent structural changes in the protein such that intramolecular phosphate migration and an oxidative elevation of proteins's phosphorylating potential result. These reactions may be of biological significance. From a practical point of view, the metal binding and release studies might have utility eventually in the nutritional and therapeutic context.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM032750-04A2
Application #
3281843
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1983-12-01
Project End
1991-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
4
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of California Santa Barbara
Department
Type
Schools of Arts and Sciences
DUNS #
City
Santa Barbara
State
CA
Country
United States
Zip Code
93106