Nature 366, 751 - 756 (30 December 1993); doi:10.1038/366751a0

Crystal structure of porcine ribonuclease inhibitor, a protein with leucine-rich repeats

Bostjan Kobe & Johann Deisenhofer

Howard Hughes Medical Institute and Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9050, USA

RIBONUCLEASE inhibitor is a cytoplasmic protein that tightly binds and inhibits ribonucleases of the pancreatic ribonuclease super-family¹. The primary sequence of this inhibitor contains leucine-rich repeats² (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 cells³ and in angiogenesis⁴. 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 / protein fold. Individual repeats constitute – 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 -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 -sheet and the loops.

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