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Modes of interaction of pleckstrin homology domains with membranes: towards a computational biochemistry of membrane recognition
- Source :
- Journal of Molecular Biology. 430(3)
- Publication Year :
- 2017
-
Abstract
- Pleckstrin homology (PH) domains mediate protein-membrane interactions by binding to phosphatidylinositol phosphate (PIP) molecules. The structural and energetic basis of selective PHPIP interactions is central to understanding many cellular processes, yet the molecular complexities of the PH-PIP interactions are largely unknown. Molecular dynamics (MD) simulations using a coarse-grained model enables estimation of free energy landscapes for the interactions of 12 different PH domains with membranes containing PIP2 or PIP3, allowing us to obtain a detailed molecular energetic understanding of the complexities of the interactions of the PH domains with PIP molecules in membranes. Distinct binding modes, corresponding to different distributions of cationic residues on the PH domain, were observed, involving PIP interactions at either the ‘canonical’ (C) and/or ‘alternate’ (A) sites. PH domains can be grouped by the relative strength of their C- and A-site interactions, revealing that a higher affinity correlates with increased C-site interactions. These simulations demonstrate that simultaneous binding of multiple PIP molecules by PH domains contributes to high affinity membrane interactions, informing our understanding of membrane recognition by PH domains in vivo.
- Subjects :
- 0301 basic medicine
Lipid Bilayers
Molecular Dynamics Simulation
03 medical and health sciences
chemistry.chemical_compound
Molecular dynamics
Phosphatidylinositol Phosphates
Structural Biology
Animals
Humans
Molecule
Phosphatidylinositol
Databases, Protein
Molecular Biology
Binding Sites
030102 biochemistry & molecular biology
Membranes, Artificial
Pleckstrin Homology Domains
Molecular Docking Simulation
Pleckstrin homology domain
Kinetics
030104 developmental biology
Membrane
chemistry
Biophysics
Thermodynamics
lipids (amino acids, peptides, and proteins)
Computational biochemistry
Protein Binding
Subjects
Details
- ISSN :
- 10898638 and 00222836
- Volume :
- 430
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of Molecular Biology
- Accession number :
- edsair.doi.dedup.....20da27082ded647e772c0210021ab479