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Related Concept Videos

Bacterial Protein Maturation01:26

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Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...
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The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
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Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
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Hsp70 and Hsp90 post-translational modifications and translating the chaperone code.

Sarah J Backe1, Jennifer A Heritz2, Mehdi Mollapour2

  • 1Department of Urology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA; Cancer Center, SUNY Upstate Medical University, Syracuse, NY, 13210.

Cell Stress & Chaperones
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Summary

Molecular chaperones like Hsp70 and Hsp90 are regulated by post-translational modifications (PTMs), forming a "chaperone code." Understanding this code is key to developing new therapies for diseases like cancer and neurodegeneration.

Keywords:
CancerCo-chaperoneHeat shock protein 70 (Hsp70)Heat shock protein 90 (Hsp90)Molecular chaperonePost-translational modification (PTM)

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Area of Science:

  • Cellular Biology
  • Biochemistry
  • Molecular Medicine

Background:

  • Molecular chaperones, including Heat Shock Protein 70 (Hsp70) and Heat Shock Protein 90 (Hsp90), are crucial for maintaining protein homeostasis (proteostasis).
  • Their functions in protein folding, stability, and cellular signaling are regulated by co-chaperones and dynamic post-translational modifications (PTMs).

Purpose of the Study:

  • To review the diverse post-translational modifications (PTMs) affecting Hsp70 and Hsp90.
  • To explore the concept of the "chaperone code" and its implications in health and disease.
  • To highlight the therapeutic potential of targeting PTMs in molecular chaperones.

Main Methods:

  • Comprehensive literature review of PTMs on Hsp70 and Hsp90.
  • Analysis of how PTMs influence chaperone ATPase activity, localization, and client interactions.
  • Discussion of the role of PTMs in cellular pathways and disease pathogenesis.

Main Results:

  • Hsp70 and Hsp90 are subject to various PTMs including phosphorylation, acetylation, methylation, ubiquitination, and glycosylation.
  • These PTMs collectively form a "chaperone code" that fine-tunes chaperone function, impacting client fate, drug sensitivity, and stress responses.
  • Combinatorial PTMs and their crosstalk add regulatory complexity, particularly relevant in cancer, neurodegeneration, and inflammation.

Conclusions:

  • The PTM landscape of Hsp70 and Hsp90 significantly impacts cellular processes and disease states.
  • Targeting the enzymes involved in writing, erasing, or reading the "chaperone code" offers promising therapeutic strategies.
  • Unlocking the chaperone code is essential for directing chaperone activity toward therapeutic benefit in various maladies.