A long-range comprehensive program is proposed for study of the structure, function, and genetic control of a series of inadequately characterized human plasma proteins, principally alpha-glycoproteins and beta-glycoproteins. Some have identified function and clinical significance and others not, but in no case is much known about their structure. Emphasis will be on determination of the amino acid sequence, disulfide bonding pattern, localization and kind of carbohydrate groups, and the combining sites of ligands such as metal ions and heme. Correlation of function and structure will be sought, and interrelationships with other plasma proteins will be investigated. Some correlations will be done in cooperation with other groups studying changes in plasma proteins in disease, their genetic polymorphism and variation, their metabolism and membrane uptake, and their three-dimensional structure. The first proteins selected for study are ceruloplasmin, a copper-containing protein with ferroxidase activity that is involved in copper metabolism and beta-glycoprotein I, a crystallizable protein of high carbohydrate content and of unknown function. Proteins under exploratory study for future investigation include: 1) the heme-binding protein hemopexin, 2) the histidine-rich alpha 2-glycoprotein that binds both heme and divalent metals, and 3) angiotensinogen (renin substrate) the precusor of angiotensin, a pressor substance probably involved in hypertension. The long range goals are to make a major contribution to knowledge about human plasma proteins, to integrate information gained from in vitro study with in vivo function, and to focus attention on characterization, quantitation, and clinical significance of this group of proteins from human blood plasma. The methods to be used include amino acid and carbohydrate analysis, amino acid sequence anlysis, immunochemical and physicochemical characterization, nuclear magnetic resonance spectroscopy, circular dichroism, and other procedures for structural study of proteins and carbohydrates.
