Characterization of PUD-1 and PUD-2, Two Proteins Up-Regulated in a Long-Lived daf-2 Mutant |
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| Authors: | Yue-He Ding Yun-Guang Du Shukun Luo Yu-Xin Li Tie-Mei Li Sawako Yoshina Xing Wang Karsten Klage Shohei Mitani Keqiong Ye Meng-Qiu Dong |
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| Institution: | 1. National Institute of Biological Sciences, Beijing, Beijing, China.; 2. Graduate Program in Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.; 3. Department of Physiology, Tokyo Women''s Medical University, Tokyo, Japan.; 4. Department of Cellular Biochemistry, Max Planck Institute of Biochemistry, Martinsried, Germany.; Ohio State University, United States of America, |
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| Abstract: | 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-Å resolution and found that both proteins adopt similar β-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 β-peptide (1-42), which further enhanced the protection conferred by daf-2(RNAi) against Aβ. |
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