Eukaryotic ribosome P-stalk and sarcin–ricin loop of 28S rRNA (P-stalk/SRL)

The eukaryotic ribosome P-stalk and the sarcin–ricin loop (SRL) of the 28S rRNA constitute a critical functional domain within the large (60S) ribosomal subunit, collectively known as the GTPase-associated center (GAC) (Grela et al., 2019, PMID: 30711536). The P-stalk is a flexible lateral arm composed of ribosomal proteins P0, P1, and P2 that recruits and activates translational GTPases like elongation factors eEF1A and eEF2 (Wortman et al., 2020, PMID: 32518182). The SRL is a highly conserved RNA motif adjacent to the P-stalk that is essential for the GTPase activity of these factors during protein synthesis (Shi et al., 2022, PMID: 35435845). This region is the primary target for Ribosome-Inactivating Proteins (RIPs) such as ricin, Shiga toxin, and saporin, which use the P-stalk as a docking site to access the SRL and catalyze the depurination of a specific adenine residue (A4324 in humans) (May et al., 2012, PMID: 22493240). This modification irreversibly inhibits the ribosome's ability to bind elongation factors, leading to a complete halt in protein synthesis and subsequent cell death. In clinical medicine, the P-stalk is a known target for autoantibodies in systemic lupus erythematosus (SLE), serving as a diagnostic biomarker (Arnett et al., 1996, PMID: 8918880). Furthermore, the potent cytotoxic activity of SRL-targeting toxins is exploited in the development of immunotoxins for oncology, where toxins are conjugated to antibodies to target specific cancer cells (Polito et al., 2016, PMID: 27135354).

Other names

GTPase-associated centerGACRibosomal factor-binding siteSRLP-protein complexRibosomal stalk60S stalk

Ribosome-inactivating proteins (RIPs) bind to the P-stalk proteins (P0, P1, P2) to facilitate their recruitment to the sarcin-ricin loop (SRL). Once at the SRL, Type II RIPs like ricin act as N-glycosylases to depurinate the A4324 residue of the 28S rRNA, while ribotoxins like alpha-sarcin act as endonucleases to cleave the phosphodiester backbone (Shi et al., 2022, PMID: 35435845). These modifications prevent the binding of elongation factors eEF1A and eEF2, thereby arresting protein synthesis and inducing apoptosis (Grela et al., 2019, PMID: 30711536).