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In complexation reactions, metal atoms or cations interact with ligands to form donor-acceptor adducts called metal complexes. Ligands that bind through one donor site are monodentate, ligands with two donor sites are bidentate, and those with more than two donor sites are polydentate ligands. For example, ethylene diamine is a bidentate ligand that binds through two nitrogen donor atoms, forming a five-membered ring. EDTA is a polydentate ligand that binds through four oxygen and two nitrogen...
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Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
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Metal ions can be separated from one another by complexation with organic ligands–the chelating agent– to form uncharged chelates. Here, the chelating agent must contain hydrophobic groups and behave as a weak acid, losing a proton to bind with the metal. Since most organic ligands used in this process are insoluble or undergo oxidation in the aqueous phase, the chelating agent is initially added to the organic phase and extracted into the aqueous phase. The metal-ligand complex is...
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In complexation reactions, metal cations are the electron pair acceptors, and the ligands are the electron pair donors. The stability of the metal complexes depends primarily on the complexing ability of the central metal ion and the nature of the ligands. Generally, the complexing ability of the metal ion depends on the size and charge of the ion. As the metal ion size increases, the stability of the metal complexes decreases, provided that the valency of the metal ion and the ligands remain...
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Ligand effects on phase separation of multivalent macromolecules.

Kiersten M Ruff1,2, Furqan Dar2,3, Rohit V Pappu1,2

  • 1Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO 63130; kiersten.ruff@wustl.edu pappu@wustl.edu.

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Ligands control cellular condensates by altering scaffold protein phase transitions. Multivalent ligands can stabilize or destabilize condensates, influencing cellular processes.

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Area of Science:

  • Biochemistry and biophysics
  • Cell biology
  • Molecular dynamics

Background:

  • Biomolecular condensates regulate cellular functions through precise spatial and temporal control.
  • Condensates form via phase transitions of multivalent scaffold macromolecules.
  • Ligands, nonscaffold molecules binding to scaffolds, modulate these phase transitions.

Purpose of the Study:

  • To elucidate the rules governing ligand-mediated control over scaffold phase behavior.
  • To understand how ligand properties influence condensate stability and structure.

Main Methods:

  • Theoretical modeling using the stickers-and-spacers model.
  • Computational analysis of ligand-scaffold interactions.
  • Investigating the effects of ligand valence and binding sites.

Main Results:

  • Ligand effects depend on valence, binding site (stickers vs. spacers), and relative affinities.
  • Monovalent ligands generally destabilize condensates.
  • Multivalent ligands can stabilize or destabilize condensates based on binding site.
  • Bipartite ligands can alter internal condensate structure without affecting stability.

Conclusions:

  • Ligand properties critically determine their impact on condensate phase behavior.
  • Measuring scaffold concentrations in dilute phases is crucial for understanding in vivo regulation.
  • This research provides a framework for predicting and controlling condensate formation and dissolution.