The PXDLS linear motif regulates circadian rhythmicity through protein-protein interactions.
Bottom Line: Our bioinformatics analysis of short linear motifs, implicated in protein interactions, reveals an enrichment of the Pro-X-Asp-Leu-Ser (PXDLS) motif within circadian transcripts.Remarkably, the motif is evolutionary conserved in the core clock protein REV-ERBα, and additional proteins implicated in the clock's function (NRIP1, CBP).Furthermore, we demonstrate that the PXDLS motifs of NRIP1 and CBP are involved in circadian rhythmicity.
Affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.Show MeSH
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Mentions: To examine the role of the PXDLS motif in the BMAL1/CLOCK–REV-ERBα interactions, we mutated the PXDLS motif of REV-ERBα (REV-ERBα P72A) and examined its binding to BMAL1. Co-immunoprecpitation experiments showed that mutation in the PXDLS motif of REV-ERBα decreased the binding of REV-ERBα to BMAL1 (Figure 6A). To further test the role of the PXDLS motif of REV-ERBα in the interaction, we examined the effect of recombinant PXDLS peptide on the binding of in vitro translated [35S] labeled REV-ERBα, to recombinant BMAL1. The binding of in vitro translated [35S] labeled REV-ERBα to recombinant BMAL1 declined in the presence of excess of PXDLS but not the mutant PXDLS peptide (Figure 6B).
Affiliation: Department of Biological Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel.