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Structural Basis for the Activity of a Cytoplasmic RNA Terminal U-transferaseStructural Basis for the Activity of a Cytoplasmic RNA Terminal U-transferase
Structural highlights
Function[CID1_SCHPO] Involved in cell cycle arrest where in association with crb2/rhp9 and chk1 it inhibits unscheduled mitosis. Publication Abstract from PubMedCytoplasmic terminal uridylyl transferases comprise a conserved family of enzymes that negatively regulate the stability or biological activity of a variety of eukaryotic RNAs, including mRNAs and tumor-suppressor let-7 microRNAs. Here we describe crystal structures of the Schizosaccharomyces pombe cytoplasmic terminal uridylyl transferase Cid1 in two apo conformers and bound to UTP. We demonstrate that a single histidine residue, conserved in mammalian Cid1 orthologs, is responsible for discrimination between UTP and ATP. We also describe a new high-affinity RNA substrate-binding mechanism of Cid1, which is essential for enzymatic activity and is mediated by three basic patches across the surface of the enzyme. Overall, our structures provide a basis for understanding the activity of Cid1 and a mechanism of UTP selectivity conserved in its human orthologs, suggesting potential implications for anticancer drug design. Structural basis for the activity of a cytoplasmic RNA terminal uridylyl transferase.,Yates LA, Fleurdepine S, Rissland OS, De Colibus L, Harlos K, Norbury CJ, Gilbert RJ Nat Struct Mol Biol. 2012 Jul 1. doi: 10.1038/nsmb.2329. PMID:22751018[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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