THE INTER-ALPHA-INHIBITOR FAMILY - FROM STRUCTURE TO REGULATION

Inter-a-inhibitor (I alpha I) and related molecules, collectively refe rred to as the I alpha I family, are a group of plasma protease inhibi tors. They display attractive features such as precursor polypeptides that give rise to mature chains with quite distinct fates and function s, and inter-chain glycosaminoglycan bonds within the various molecule s. The discovery of an ever growing number of such molecules has raise d pertinent questions about their pathophysiological functions. The kn owledge of this family has long been structure-oriented, whereas the s tructure/function and structure/regulation relationships of the family members and their genes have been largely ignored. These relationship s are now being elucidated in events such as gene transcription, precu rsor processing, changes in plasma protein levels in health and diseas e and binding capacities that involve hyaluronan as well as other plas ma proteins as ligands. This review presents some recent progress made in these fields that paves the way for an understanding of the functi ons of I alpha I family members in vivo. Finally, given the wealth of heterogeneous, complicated and sometimes contradictory nomenclatures a nd acronyms currently in use for this family, a new, uniform, nomencla ture is proposed for I alpha I family genes, precursor polypeptides an d assembled proteins.