4E7X

Structural Basis for the Activity of a Cytoplasmic RNA Terminal U-transferase

Summary for 4E7X

• Entry DOI: 10.2210/pdb4e7x/pdb
• Related: 4E80 4E8F
• Descriptor: Poly(A) RNA polymerase protein cid1, ACETATE ION (3 entities in total)
• Functional Keywords: beta polymerase-like nucleotidyl transferase, terminal uridine transferase, utp, rna, cytoplasmic, transferase
• Biological source: Schizosaccharomyces pombe 972h- (Fission yeast)
• Cellular location: Cytoplasm : O13833
• Total number of polymer chains: 4
• Total formula weight: 185515.41

Authors

Yates, L.A.,Fleurdepine, S.,Rissland, O.S.,DeColibus, L.,Harlos, K.,Norbury, C.J.,Gilbert, R.J.C. (deposition date: 2012-03-19, release date: 2012-07-04, Last modification date: 2024-02-28)

Primary citation

Yates, L.A.,Fleurdepine, S.,Rissland, O.S.,De Colibus, L.,Harlos, K.,Norbury, C.J.,Gilbert, R.J.
Structural basis for the activity of a cytoplasmic RNA terminal uridylyl transferase.
Nat.Struct.Mol.Biol., 19:782-787, 2012

PubMed Abstract: Cytoplasmic 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.

PubMed: 22751018
DOI: 10.1038/nsmb.2329

Experimental method

X-RAY DIFFRACTION (3.2 Å)