Arginine ADP-ribosylation mechanism based on structural snapshots of iota-toxin and actin complex.
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Tsurumura T, Tsumori Y, Qiu H, Oda M, Sakurai J, Nagahama M, Tsuge H
Arginine ADP-ribosylation mechanism based on structural snapshots of iota-toxin and actin complex.
Proc Natl Acad Sci U S A. 2013 Mar 12;110(11):4267-72. doi: 10.1073/pnas.1217227110. Epub 2013 Feb 4.
- PubMed ID
- 23382240 [ View in PubMed]
- Abstract
Clostridium perfringens iota-toxin (Ia) mono-ADP ribosylates Arg177 of actin, leading to cytoskeletal disorganization and cell death. To fully understand the reaction mechanism of arginine-specific mono-ADP ribosyl transferase, the structure of the toxin-substrate protein complex must be characterized. Recently, we solved the crystal structure of Ia in complex with actin and the nonhydrolyzable NAD(+) analog betaTAD (thiazole-4-carboxamide adenine dinucleotide); however, the structures of the NAD(+)-bound form (NAD(+)-Ia-actin) and the ADP ribosylated form [Ia-ADP ribosylated (ADPR)-actin] remain unclear. Accidentally, we found that ethylene glycol as cryo-protectant inhibits ADP ribosylation and crystallized the NAD(+)-Ia-actin complex. Here we report high-resolution structures of NAD(+)-Ia-actin and Ia-ADPR-actin obtained by soaking apo-Ia-actin crystal with NAD(+) under different conditions. The structures of NAD(+)-Ia-actin and Ia-ADPR-actin represent the pre- and postreaction states, respectively. By assigning the betaTAD-Ia-actin structure to the transition state, the strain-alleviation model of ADP ribosylation, which we proposed previously, is experimentally confirmed and improved. Moreover, this reaction mechanism appears to be applicable not only to Ia but also to other ADP ribosyltransferases.