Overlapping recognition determinants within the ssrA degradation tag allow modulation of proteolysis

AUTOR(ES)

Flynn, Julia M.

FONTE

The National Academy of Sciences

RESUMO

The ssrA tag, an 11-aa peptide added to the C terminus of proteins stalled during translation, targets proteins for degradation by ClpXP and ClpAP. Mutational analysis of the ssrA tag reveals independent, but overlapping determinants for its interactions with ClpX, ClpA, and SspB, a specificity-enhancing factor for ClpX. ClpX interacts with residues 9–11 at the C terminus of the tag, whereas ClpA recognizes positions 8–10 in addition to residues 1–2 at the N terminus. SspB interacts with residues 1–4 and 7, N-terminal to the ClpX-binding determinants, but overlapping the ClpA determinants. As a result, SspB and ClpX work together to recognize ssrA-tagged substrates efficiently, whereas SspB inhibits recognition of these substrates by ClpA. Thus, dissection of the recognition signals within the ssrA tag provides insight into how multiple proteins function in concert to modulate proteolysis.

Documentos Relacionados

• RNase E is required for the maturation of ssrA RNA and normal ssrA RNA peptide-tagging activity
• Stop codons preceded by rare arginine codons are efficient determinants of SsrA tagging in Escherichia coli
• The tRNA function of SsrA contributes to controlling repression of bacteriophage Mu prophage
• ssrA (tmRNA) Plays a Role in Salmonella enterica Serovar Typhimurium Pathogenesis
• The SopEΦ Phage Integrates into the ssrA Gene of Salmonella enterica Serovar Typhimurium A36 and Is Closely Related to the Fels-2 Prophage