CRYSTAL-STRUCTURE OF PORCINE RIBONUCLEASE INHIBITOR, A PROTEIN WITH LEUCINE-RICH REPEATS

RIBONUCLEASE inhibitor is a cytoplasmic protein that tightly binds and inhibits ribonucleases of the pancreatic ribonuclease superfamily1. T he primary sequence of this inhibitor contains leucine-rich repeats2 ( LRRs); these motifs are present in many proteins that participate in p rotein-protein interactions and have different functions and cellular locations. In vivo, ribonuclease inhibitor may have a role in the regu lation of RNA turnover in mammalian cells3 and in angiogenesis4. To de fine the structural features of LRR proteins and to understand better the nature of the tight interaction of ribonuclease inhibitor with rib onucleases, we have determined the crystal structure of the porcine in hibitor. To our knowledge, this is the first three-dimensional structu re of a protein containing LRRs and represents a new class of alpha/be ta protein fold. Individual repeats constitute beta-alpha structural u nits that probably also occur in other proteins containing LRRs. The n on-globular shape of the structure and the exposed face of the paralle l beta-sheet may explain why LRRs are used to achieve strong protein-p rotein interactions. A possible ribonuclease-binding region incorporat es the surface formed by the parallel beta-sheet and the betaalpha loo ps.