title: Crystal structure of porcine ribonuclease inhibitor, a protein with leucine-rich repeats.
abstract: Ribonuclease inhibitor is a cytoplasmic protein that tightly binds and inhibits ribonucleases of the pancreatic ribonuclease superfamily. The primary sequence of this inhibitor contains leucine-rich repeats (LRRs); these motifs are present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. In vivo, ribonuclease inhibitor may have a role in the regulation of RNA turnover in mammalian cells and in angiogenesis. To define the structural features of LRR proteins and to understand better the nature of the tight interaction of ribonuclease inhibitor with ribonucleases, we have determined the crystal structure of the porcine inhibitor. To our knowledge, this is the first three-dimensional structure of a protein containing LRRs and represents a new class of alpha/beta protein fold. Individual repeats constitute beta-alpha structural units that probably also occur in other proteins containing LRRs. The non-globular shape of the structure and the exposed face of the parallel beta-sheet may explain why LRRs are used to achieve strong protein-protein interactions. A possible ribonuclease-binding region incorporates the surface formed by the parallel beta-sheet and the beta alpha loops.
authors.affiliation: Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas 75235-9050.
authors.forename: B
authors.initials: B
authors.lastname: Kobe
authors.forename: J
authors.initials: J
authors.lastname: Deisenhofer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003196:Computer Graphics; D003461:Crystallography; D047908:Intracellular Signaling Peptides and Proteins; D007930:Leucine / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*; D012260:Ribonucleases / Q000037:antagonists & inhibitors*; D013552:Swine
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C066953:ribonuclease inhibitor, porcine; D012260:Ribonucleases; D007930:Leucine