The structure of a yeast RNA-editing deaminase provides insight into the fold and function of activation-induced deaminase and APOBEC-1
| Autor: | Kefang Xie, Andrew T. Torelli, Harold C. Smith, Mark P. Sowden, Joseph E. Wedekind, Geoffrey S. C. Dance |
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| Rok vydání: | 2004 |
| Předmět: |
Models
Molecular APOBEC Protein Folding Saccharomyces cerevisiae Proteins Protein Conformation APOBEC-1 Deaminase Somatic hypermutation Saccharomyces cerevisiae Biology Crystallography X-Ray Cytidine Deaminase Activation-induced (cytidine) deaminase Humans Binding site Binding Sites Multidisciplinary RNA Syndrome Cytidine deaminase Biological Sciences Immunoglobulin M Biochemistry RNA editing Mutation biology.protein RNA Editing |
| Zdroj: | Proceedings of the National Academy of Sciences. 101:8114-8119 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0400493101 |
| Popis: | Activation-induced deaminase (AID) uses base deamination for class-switch recombination and somatic hypermutation and is related to the mammalian RNA-editing enzyme apolipoprotein B editing catalytic subunit 1 (APOBEC-1). CDD1 is a yeast ortholog of APOBEC-1 that exhibits cytidine deaminase and RNA-editing activity. Here, we present the crystal structure of CDD1 at 2.0-Å resolution and its use in comparative modeling of APOBEC-1 and AID. The models explain dimerization and the need for trans-acting loops that contribute to active site formation. Substrate selectivity appears to be regulated by a central active site “flap” whose size and flexibility accommodate large substrates in contrast to deaminases of pyrimidine metabolism that bind only small nucleosides or free bases. Most importantly, the results suggested both AID and APOBEC-1 are equally likely to bind single-stranded DNA or RNA, which has implications for the identification of natural AID targets. |
| Databáze: | OpenAIRE |
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