HBS1L-PELO protein complex (HBS1L-PELO)

The HBS1L-PELO protein complex is a fundamental component of the eukaryotic mRNA surveillance system, specifically mediating the No-Go Decay (NGD) and Non-Stop Decay (NSD) pathways (UniProt Q9Y450, Q9BRX2). This complex is composed of the HBS1-like protein (HBS1L), a member of the translational GTPase family, and Pelota (PELO), which serves as a structural mimic of the eukaryotic release factor eRF1 (Pisareva et al., 2011). Its primary biological role is to recognize and rescue ribosomes that have stalled on problematic mRNA templates, such as those containing strong secondary structures or lacking a stop codon (Becker et al., 2011). Upon binding to the stalled ribosome's A-site, the complex recruits the ABCE1 ATPase to facilitate the dissociation of the 80S ribosome into its 40S and 60S subunits, thereby enabling the degradation of the faulty mRNA and the recycling of ribosomal components (Juszkiewicz & Hegde, 2017). In a clinical context, the HBS1L-PELO complex is significantly linked to the regulation of fetal hemoglobin (HbF) levels, making it a point of interest for treating hemoglobinopathies like beta-thalassemia and sickle cell disease (Menzel et al., 2007). Furthermore, its involvement in maintaining proteostasis suggests potential roles in neurodegenerative diseases and cancer, where ribosome stalling is often exacerbated. While there are currently no FDA-approved drugs that directly target this complex, it remains an active area of research for developing novel antiviral and protein-quality-control-modulating therapies.

Other names

Pelota-Hbs1 complexPELO-HBS1L complexDom34-Hbs1 complex

Facilitation of stalled 80S ribosome dissociation and recruitment of ABCE1 ATPase to the ribosome A-site