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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Amyloid beta-Peptides / pharmacology
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Animals
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Caenorhabditis elegans / physiology*
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Caenorhabditis elegans Proteins / chemistry
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Crystallography, X-Ray
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Forkhead Transcription Factors
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Gene Expression
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Hydrophobic and Hydrophilic Interactions
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Longevity
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Models, Molecular
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Molecular Sequence Data
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Peptide Fragments / pharmacology
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Protein Multimerization
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Protein Structure, Quaternary
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Receptor, Insulin / genetics*
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Sequence Homology, Amino Acid
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Stress, Physiological
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Transcription Factors / metabolism
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Up-Regulation
Substances
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Amyloid beta-Peptides
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Caenorhabditis elegans Proteins
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Forkhead Transcription Factors
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Peptide Fragments
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Transcription Factors
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amyloid beta-protein (1-42)
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daf-16 protein, C elegans
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DAF-2 protein, C elegans
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Receptor, Insulin
Grants and funding
The Ministry of Science and Technology of China (863 grant 2007AA02Z1A7 and 973 grant 2010CB835203 to M-QD; 863 grant 2008AA022310 and 973 grant 2010CB835402 to KY) and the municipal government of Beijing funded this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.