Molecular Biology

Isomerization of the Peptide Bond

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Science  11 Aug 2000:
Vol. 289, Issue 5481, pp. 833
DOI: 10.1126/science.289.5481.833d

Prolyl isomerases are most familiar as the targets of the immunosuppressive drugs cyclosporin and FK506, which bind, respectively, to cyclophilins and FK506-binding proteins (FKBPs). An as yet intractable puzzle has been the cellular function of these enzymes, which generally are not essential for viability.

Wu et al. have studied a third class of prolyl isomerases, typified by Ess1 which is essential for growth in yeast. Unlike the other two kinds, Ess1 contains a WW domain (so-called for two invariant tryptophans) in addition to the catalytic domain; the WW domain is known to interact with phosphoserine-proline sequences. From a combination of genetic (to identify suppressors) and biochemical (to characterize interactions) experiments, they conclude that Ess1 functions by binding to the C-terminal domain (CTD) of RNA polymerase. Thus, Ess1 would control the recruitment of transcriptional regulatory factors via their interactions with the CTD—which is known to include many copies of a seven-residue repeat containing two serine-proline motifs.

Arévalo-Rodríguez et al. have examined the interactions of cyclophilin and Ess1 with components of a chromatin remodeling complex, while Verdecia et al. describe the structure of a WW domain bound to the doubly phosphorylated heptad repeat. — GJC

EMBO J.19, 3727 (2000); EMBO J.19, 3739 (2000); Nature Struct. Biol.7, 639 (2000).

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