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Journal Article

Characterization of PUD-1 and PUD-2, Two Proteins Up-Regulated in a Long-Lived daf-2 Mutant


Klage,  Karsten
Hartl, Franz-Ulrich / Cellular Biochemistry, Max Planck Institute of Biochemistry, Max Planck Society;

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Ding, Y.-H., Du, Y.-G., Luo, S., Li, Y.-X., Li, T.-M., Yoshina, S., et al. (2013). Characterization of PUD-1 and PUD-2, Two Proteins Up-Regulated in a Long-Lived daf-2 Mutant. PLOS ONE, 8(6): e67158. doi:10.1371/journal.pone.0067158.

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C. elegans PUD-1 and PUD-2, two proteins up-regulated in daf-2(loss-of-function) (PUD), are homologous 17-kD proteins with a large abundance increase in long-lived daf-2 mutant animals of reduced insulin signaling. In this study, we show that both PUD-1 and PUD-2 are abundantly expressed in the intestine and hypodermis, and form a heterodimer. We have solved their crystal structure to 1.9-angstrom resolution and found that both proteins adopt similar beta-sandwich folds in the V-shaped dimer. In contrast, their homologs PUD-3, PUD-4, PUDL-1 and PUDL-2 are all monomeric proteins with distinct expression patterns in C. elegans. Thus, the PUD-1/PUD-2 heterodimer probably has a function distinct from their family members. Neither overexpression nor deletion of pud-1 and pud-2 affected the lifespan of WT or daf-2 mutant animals, suggesting that their induction in daf-2 worms does not contribute to longevity. Curiously, deletion of pud-1 and pud-2 was associated with a protective effect against paralysis induced by the amyloid beta-peptide (1-42), which further enhanced the protection conferred by daf-2(RNAi) against A beta.