Heat shock protein 90 regulates development in Dictyostelium discoideum

Journal of Molecular Biology
Ritwick SawarkarUtpal Tatu

Abstract

Cytosolic heat shock protein 90 (Hsp90) has been implicated in diverse biological processes such as protein folding, cell cycle control, signal transduction, development, and morphological evolution. Model systems available for studying Hsp90 function either allow ease of manipulation for biochemical studies or facilitate a phenomenological study of its role in influencing phenotype. In this work, we have explored the use of the cellular slime mold Dictyostelium discoideum to examine cellular functions of Hsp90 in relation to its multicellular development. In addition to cloning, purification, biochemical characterization, and examination of its crystal structure, our studies, using a pharmacological inhibitor of Hsp90, demonstrate a role for the cytoplasmic isoform (HspD) in D. discoideum development. Inhibition of HspD function using geldanamycin (GA) resulted in delayed aggregation and arrest of D. discoideum development at the 'mound' stage. Crystal structure of the amino-terminal domain of HspD showed a binding pocket similar to that described for yeast Hsp90. Fluorescence spectroscopy, as well as GA-coupled beads affinity pulldown, confirmed a specific interaction between HspD and GA. The results presented here provide an...Continue Reading

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Citations

Jan 7, 2011·The Journal of Biological Chemistry·Rishi Kumar NageshanUtpal Tatu
May 3, 2014·PLoS Neglected Tropical Diseases·Rishi Kumar NageshanUtpal Tatu
Jul 7, 2009·Journal of Molecular Biology·Ritwick SawarkarVidyanand Nanjundiah
Mar 31, 2009·Current Biology : CB·Rebecca S ShapiroLeah E Cowen
Dec 27, 2011·Biochimica Et Biophysica Acta·Nainita RoyUtpal Tatu
May 14, 2014·Antimicrobial Agents and Chemotherapy·Anjan DebnathJames H McKerrow
Jun 10, 2015·Acta Crystallographica. Section F, Structural Biology Communications·Swetha Raman, Kaza Suguna
Aug 5, 2021·Journal of Enzyme Inhibition and Medicinal Chemistry·Natalia SkrzypczakPiotr Przybylski

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