2xl1
From Proteopedia
Structural basis of translational stalling by human cytomegalovirus (hCMV) and fungal arginine attenuator peptide (AAP)
Structural highlights
Function[AAP_NEUCR] Arginine attenuator peptide (AAP) that has a regulatory role in the production of arginine-specific carbamoyl phosphate synthetase. Encoded by an upstream open reading frame (uORF) within the 5'-leader region of arginine-specific carbamoyl phosphate synthetase small chain (arg-2) mRNA, it attenuates the translation of the downstream arg-2 ORF. In the presence of high concentrations of arginine, ribosomes translating the uORF encoding AAP stall at the termination codon, resulting in reduced translation from the downstream arg-2 initiation codon.[1] [2] [3] [4] Publication Abstract from PubMedSpecific regulatory nascent chains establish direct interactions with the ribosomal tunnel, leading to translational stalling. Despite a wealth of biochemical data, structural insight into the mechanism of translational stalling in eukaryotes is still lacking. Here we use cryo-electron microscopy to visualize eukaryotic ribosomes stalled during the translation of two diverse regulatory peptides: the fungal arginine attenuator peptide (AAP) and the human cytomegalovirus (hCMV) gp48 upstream open reading frame 2 (uORF2). The C terminus of the AAP appears to be compacted adjacent to the peptidyl transferase center (PTC). Both nascent chains interact with ribosomal proteins L4 and L17 at tunnel constriction in a distinct fashion. Significant changes at the PTC were observed: the eukaryotic-specific loop of ribosomal protein L10e establishes direct contact with the CCA end of the peptidyl-tRNA (P-tRNA), which may be critical for silencing of the PTC during translational stalling. Our findings provide direct structural insight into two distinct eukaryotic stalling processes. Structural basis for translational stalling by human cytomegalovirus and fungal arginine attenuator peptide.,Bhushan S, Meyer H, Starosta AL, Becker T, Mielke T, Berninghausen O, Sattler M, Wilson DN, Beckmann R Mol Cell. 2010 Oct 8;40(1):138-46. PMID:20932481[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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