4H0Y

Crystal structure of NAD+-Ia(E380S)-actin complex

Summary for 4H0Y

• Entry DOI: 10.2210/pdb4h0y/pdb
• Related: 1GIQ 1GIR 3BUZ 4GY2 4H03 4H0T 4H0V 4H0X
• Descriptor: Iota toxin component Ia, Actin, alpha skeletal muscle, NICOTINAMIDE-ADENINE-DINUCLEOTIDE, ... (9 entities in total)
• Functional Keywords: adp-ribosyltransferase, toxin-structural protein complex, toxin/structural protein
• Biological source: Clostridium perfringens; More
• Cellular location: Cytoplasm, cytoskeleton: P68135
• Total number of polymer chains: 2
• Total formula weight: 94994.50

Authors

Tsurumura, T.,Oda, M.,Nagahama, M.,Tsuge, H. (deposition date: 2012-09-10, release date: 2013-02-20, Last modification date: 2023-11-08)

Primary citation

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.USA, 110:4267-4272, 2013

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 βTAD (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 βTAD-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.

PubMed: 23382240
DOI: 10.1073/pnas.1217227110

Experimental method

X-RAY DIFFRACTION (1.94 Å)