5DDZ: Crystal Structure Of The Rta-c10-p2 Complex

Citation:
Abstract
Ricin is a type II ribosome-inactivating protein (RIP) that depurinates A4324 at the sarcin-ricin loop of 28 S ribosomal RNA (rRNA), thus inactivating the ribosome by preventing elongation factors from binding to the GTPase activation centre. Recent studies have disclosed that the conserved C-terminal domain (CTD) of eukaryotic ribosomal P stalk proteins is involved in the process that RIPs target ribosome. However, the details of the molecular interaction between ricin and P stalk proteins remain unknown. Here, we report the structure of ricin-A chain (RTA) in a complex with the CTD of the human ribosomal protein P2. The structure shows that the Phe111, Leu113 and Phe114 residues of P2 insert into a hydrophobic pocket formed by the Tyr183, Arg235, Phe240 and Ile251 residues of RTA, while Asp115 of P2 forms hydrogen bonds with Arg235 of RTA. The key residues in RTA and P2 for complex formation were mutated, and their importance was determined by pull-down assays. The results from cell-free translation assays further confirmed that the interaction with P stalk proteins is essential for the inhibition of protein synthesis by RTA. Taken together, our results provide a structural basis that will improve our understanding of the process by which ricin targets the ribosome, which will benefit the development of effective small-molecule inhibitors for use as therapeutic agents.
PDB ID: 5DDZDownload
MMDB ID: 142768
PDB Deposition Date: 2015/8/25
Updated in MMDB: 2016/12
Experimental Method:
x-ray diffraction
Resolution: 1.5  Å
Source Organism:
Homo sapiens
Similar Structures:
Biological Unit for 5DDZ: dimeric; determined by author and by software (PISA)
Molecular Components in 5DDZ
Label Count Molecule
Proteins (2 molecules)
1
Ricin(Gene symbol: LOC8261245)
Molecule annotation
1
60S Acidic Ribosomal Protein P2(Gene symbol: RPLP2)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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