Characterization of an aldolase-binding site in the Wiskott-Aldrich syndrome protein
| Autor: | Victor Nussenzweig, Deepak Penesetti, Carlos A. Buscaglia, Mingyuan Tao |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
DNA
Complementary Recombinant Fusion Proteins Acid Phosphatase Molecular Sequence Data macromolecular substances Biochemistry Fructose-Bisphosphate Aldolase Humans Amino Acid Sequence Binding site Cloning Molecular Molecular Biology Peptide sequence Actin chemistry.chemical_classification Binding Sites biology Tartrate-Resistant Acid Phosphatase Wiskott–Aldrich syndrome protein Aldolase A Cell Biology Transmembrane protein Peptide Fragments Isoenzymes Kinetics Enzyme chemistry Cytoplasm Mutation biology.protein Wiskott-Aldrich Syndrome Protein |
| Zdroj: | The Journal of biological chemistry. 281(3) |
| ISSN: | 0021-9258 |
| Popis: | The thrombospondin-related anonymous protein (TRAP) is an essential transmembrane molecule in Plasmodium sporozoites. TRAP displays adhesive motifs on the extracellular portion, whereas its cytoplasmic tail connects to actin via aldolase, thus driving parasite motility and host cell invasion. The minimal requirements for the TRAP binding to aldolase were scanned here and found to be shared by different human proteins, including the Wiskott-Aldrich syndrome protein (WASp) family members. In vitro and in vivo binding of WASp members to aldolase was characterized by biochemical, deletion mapping, mutagenesis, and co-immunoprecipitation studies. As in the case of TRAP, the binding of WASp to aldolase is competitively inhibited by the enzyme substrate/products. Furthermore, TRAP and WASp, but not other unrelated aldolase binders, compete for the binding to the enzyme in vitro. Together, our results define a conserved aldolase binding motif in the WASp family members and suggest that aldolase modulates the motility and actin dynamics of mammalian cells. These findings along with the presence of similar aldolase binding motifs in additional human proteins, some of which indeed interact with aldolase in pull-down assays, suggest supplementary, non-glycolytic roles for this enzyme. |
| Databáze: | OpenAIRE |
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