Principles which govern surface recognition, intra- and intermolecular assembly and function of peptides and proteins are being studied, currently for neurophysin-neuropeptide hormone complexes and their precursors as well as for several other experimentally advantageous peptides and proteins. Molecular recognition by peptides and proteins underlies essentially all biological functions of these substances, emphasizing the importance of understanding surface organization and dynamics in determining molecular order and function. This issue has been addressed with the neurohypophysial hormones oxytocin and vasopressin and associated neurophysins, which form cooperative peptide-protein complexes that act as storage forms for the polypeptides in neurosecretory granules. The nature and structural interrelationships between the self-association and hormone binding surfaces in neurophysins that give rise to cooperative complexes have been studied, including evaluation of these interactions for molecular species isolated both from various neuroendocrine sites and in vitro by sequence modification, semisynthesis, and cell-free translation. Separately, underlying principles which determine surface recognition and consequent molecular order have been evaluated by studying the effect of synthetic sequence modeling of ribonuclease S-peptide on formation of functional ribonuclease-S. The structure of a modeled semisynthetic ribonuclease-S has been solved to high resolution by X-ray diffraction analysis. This structure is being used as a basis to examine rules of protein self-assembly and to establish general guidelines for protein engineering. In addition, the extent to which molecular order and segmental flexibility in proteins control limited proteolysis is being studied with the enzyme thermolysin. Correlation of proteolysis, domain assembly, and flexibility is being used to better understand the regulation of enzymatic processing of endocrine """"""""multi-domain"""""""" precursors.

Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Arthritis, Diabetes, Digestive & Kid Dis
Department
Type
DUNS #
City
State
Country
United States
Zip Code