Molecular mechanism of phosphoinositides' specificity for the inwardly rectifying potassium channel Kir2.2† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c8sc01284a

We investigated the binding mechanism of PI(4,5)P2 and variants on the inwardly rectifying potassium channel, Kir2.2. Our results not only demonstrated the molecular origin for their binding specificity, but also revealed the major driving forces.

• Publication year

  2018

• Venue

  Chemical Science

• Publication date

  2018-09-05

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1039/c8sc01284aPMID 30542582PMCID 6247517
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Exploring the Nanotoxicology of MoS2: A Study on the Interaction of MoS2 Nanoflakes and K+ Channels.

  2017cited by this paper
• Mechanism of Divalent-Ion-Induced Charge Inversion of Bacterial Membranes.

  2016cited by this paper
• The Molecular Mechanism of Opening the Helix Bundle Crossing (HBC) Gate of a Kir Channel

  2016cited by this paper
• Phosphoinositides regulate ion channels.

  2015cited by this paper
• Molecular recognition of metabotropic glutamate receptor type 1 (mGluR1): synergistic understanding with free energy perturbation and linear response modeling.

  2014cited by this paper
• Secondary anionic phospholipid binding site and gating mechanism in Kir2.1 inward rectifier channels

  2013cited by this paper
• Scalable Molecular Dynamics with NAMD on Blue Gene / L

  2012cited by this paper
• Mechanism of Voltage Gating in Potassium Channels

  2012cited by this paper
• The Cytosolic GH Loop Regulates the Phosphatidylinositol 4,5-Bisphosphate-induced Gating Kinetics of Kir2 Channels*

  2012cited by this paper
• The molecular mechanism by which PIP(2) opens the intracellular G-loop gate of a Kir3.1 channel.

  2012cited by this paper
• Optimization of the additive CHARMM all-atom protein force field targeting improved sampling of the backbone φ, ψ and side-chain χ(1) and χ(2) dihedral angles.

  2012cited by this paper
• Free-energy simulations reveal that both hydrophobic and polar interactions are important for influenza hemagglutinin antibody binding.

  2012cited by this paper
• Structural basis of PIP2 activation of the classical inward rectifier K+ channel Kir2.2

  2011cited by this paper
• Crystal structure of the mammalian GIRK2 K+ channel and gating regulation by G proteins, PIP2, and sodium.

  2011cited by this paper
• Intermediate states of the Kv1.2 voltage sensor from atomistic molecular dynamics simulations

  2011cited by this paper
• Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types.

  2010cited by this paper
• Domain reorientation and rotation of an intracellular assembly regulate conduction in Kir potassium channels.

  2010cited by this paper
• How Highly Charged Anionic Lipids Bind and Regulate Ion Channels

  2008cited by this paper
• CHARMM‐GUI: A web‐based graphical user interface for CHARMM

  2008cited by this paper
• PIP2 is a necessary cofactor for ion channel function: how and why?

  2008cited by this paper
• Scalable molecular dynamics with NAMD on the IBM Blue Gene/L system

  2008cited by this paper
• Random walk in orthogonal space to achieve efficient free-energy simulation of complex systems

  2008cited by this paper
• Diverse Kir modulators act in close proximity to residues implicated in phosphoinositide binding

  2007cited by this paper
• Complex roles of PIP2 in the regulation of ion channels and transporters.

  2007cited by this paper
• Regulation of ion transport proteins by membrane phosphoinositides

  2007cited by this paper
• Molecular characteristics of phosphoinositide binding

  2007cited by this paper
• Phosphoinositide-mediated gating of inwardly rectifying K+ channels

  2007cited by this paper
• Activation of inwardly rectifying potassium (Kir) channels by phosphatidylinosital-4,5-bisphosphate (PIP2): interaction with other regulatory ligands.

  2007cited by this paper
• Blue Matter: Strong Scaling of Molecular Dynamics on Blue Gene/L

  2006cited by this paper
• Scalable molecular dynamics with NAMD

  2005cited by this paper
• Regulation of ion channels by phosphatidylinositol 4,5-bisphosphate.

  2005cited by this paper
• Regulation of cardiac inwardly rectifying potassium channels by membrane lipid metabolism.

  2003cited by this paper
• Specificity of activation by phosphoinositides determines lipid regulation of Kir channels

  2003cited by this paper
• Alterations in conserved Kir channel-PIP2 interactions underlie channelopathies.

  2002cited by this paper
• The Complex and Intriguing Lives of PIP2 with Ion Channels and Transporters

  2001cited by this paper
• Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid

  1999cited by this paper
• Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gβγ

  1998cited by this paper
• Membrane phospholipid control of nucleotide sensitivity of KATP channels.

  1998cited by this paper
• Cytoplasmic ATP-dependent regulation of ion transporters and channels: mechanisms and messengers.

  1997cited by this paper
• Regulation of Cardiac Na+,Ca2+ Exchange and KATP Potassium Channels by PIP2

  1996cited by this paper
• Separation‐shifted scaling, a new scaling method for Lennard‐Jones interactions in thermodynamic integration

  1994cited by this paper
• Avoiding singularities and numerical instabilities in free energy calculations based on molecular simulations

  1994cited by this paper
• Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems

  1993cited by this paper
• Comparison of simple potential functions for simulating liquid water

  1983cited by this paper

• Revealing Topological Barriers against Knot Untying in Thermal and Mechanical Protein Unfolding by Molecular Dynamics Simulations

  2021cites this paper