2xl1

From Proteopedia

Structural basis of translational stalling by human cytomegalovirus (hCMV) and fungal arginine attenuator peptide (AAP)

Structural highlights

2xl1 is a 1 chain structure with sequence from Neurospora crassa. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 PubMed

Specific 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

↑ Wang Z, Gaba A, Sachs MS. A highly conserved mechanism of regulated ribosome stalling mediated by fungal arginine attenuator peptides that appears independent of the charging status of arginyl-tRNAs. J Biol Chem. 1999 Dec 31;274(53):37565-74. PMID:10608810
↑ Luo Z, Sachs MS. Role of an upstream open reading frame in mediating arginine-specific translational control in Neurospora crassa. J Bacteriol. 1996 Apr;178(8):2172-7. PMID:8636015
↑ Wang Z, Sachs MS. Ribosome stalling is responsible for arginine-specific translational attenuation in Neurospora crassa. Mol Cell Biol. 1997 Sep;17(9):4904-13. PMID:9271370
↑ Wang Z, Fang P, Sachs MS. The evolutionarily conserved eukaryotic arginine attenuator peptide regulates the movement of ribosomes that have translated it. Mol Cell Biol. 1998 Dec;18(12):7528-36. PMID:9819438
↑ Bhushan S, Meyer H, Starosta AL, Becker T, Mielke T, Berninghausen O, Sattler M, Wilson DN, Beckmann R. Structural basis for translational stalling by human cytomegalovirus and fungal arginine attenuator peptide. Mol Cell. 2010 Oct 8;40(1):138-46. PMID:20932481 doi:10.1016/j.molcel.2010.09.009