Turning White Matter “Inside-Out” by Hyper-deimination of Myelin Basic Protein (MBP)

Harauz, George

doi:10.1007/978-3-319-58244-3_19

Cited by 2 publications

(2 citation statements)

References 301 publications

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“…We are aware that this is not an entirely pure preparation and differs somewhat from protein derived from human brain . Especially, the balance of post-translational modifications of MBP is altered in MS, possibly as one of the earlier molecular events, resulting in a preponderance of hyper-deiminated MBP of reduced net positive charge. − The pattern of modifications results in different modes of protein association with myelin-like membranes. ,, Pure recombinant forms representing the unmodified and deiminated forms of MBP have been used for many previous biophysical studies. ,, Their analysis represents a logical next step for exploitation of our experimental system established here.…”

Section: Discussionmentioning

confidence: 99%

Interaction of Myelin Basic Protein with Myelin-like Lipid Monolayers at Air–Water Interface

et al. 2018

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Interaction of myelin basic protein (MBP) and the cytoplasmic leaflets of the oligodendrocyte membrane is essential for the formation and compaction of the myelin sheath of the central nervous system and is altered aberrantly and implicated in the pathogenesis of neurodegenerative diseases like multiple sclerosis. To gain more detailed insights into this interaction, the adsorption of MBP to model lipid monolayers of similar composition to the myelin of the central nervous system was studied at the air-water interface with monolayer adsorption experiments. Measuring the surface pressure and the related maximum insertion pressure of MBP for different myelin-like lipid monolayers provided information about the specific role of each of the single lipids in the myelin. Depending on the ratio of negatively charged lipids to uncharged lipids and the distance between charges, the adsorption process was found to be determined by two counteracting effects: (i) protein incorporation, resulting in an increasing surface pressure and (ii) lipid condensation due to electrostatic interaction between the positively charged protein and negatively charged lipids, resulting in a decreasing surface pressure. Although electrostatic interactions led to high insertion pressures, the associated lipid condensation lowered the fluidity of the myelin-like monolayer.

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Section: Discussionmentioning

confidence: 99%

Interaction of Myelin Basic Protein with Myelin-like Lipid Monolayers at Air–Water Interface

et al. 2018

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“…). It has been suggested that mis‐steps in these signaling networks during myelin development may result in structurally weakened segments of myelin from which damage can readily propagate …”

Section: Introductionmentioning

confidence: 99%

Docking and molecular dynamics simulations of the Fyn‐SH3 domain with free and phospholipid bilayer‐associated 18.5‐kDa myelin basic protein (MBP)—Insights into a noncanonical and fuzzy interaction

2017

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RUNNING TITLE: Docking/MD of MBP with Fyn-SH3 in aqueous and membrane environments.KEYWORDS: amphipathic α-helix, poly-proline type II (PPII), Fyn-SH3, intrinsicallydisordered protein (IDP); myelin basic protein (MBP); molecular dynamics (MD) simulations; molecular recognition fragment (MoRF); GROMACS; HIGHLIGHTS:• Myelin basic protein (18.5-kDa MBP) has 3 membrane-associated amphipathic α-helices • Proline-rich region (P93-P98) participates in MBP/Fyn-SH3 interaction over 50-ns MD • Energetically-favorable MBP/Fyn-SH3 interaction in aqueous and membrane contexts • Docking complemented by MD led to a more comprehensive interaction model 2 ABSTRACTThe molecular details of the association between the human Fyn-SH3 domain, and the fragment of 18.5-kDa myelin basic protein (MBP) spanning residues S38-S107 (denoted as xα2-peptide, murine sequence numbering), were studied in silico via docking and molecular dynamics over 50-ns trajectories. The results show that interaction between the two proteins is energetically favorable and heavily-dependent on the MBP proline-rich region (P93-P98) in both aqueous and membrane environments. In aqueous conditions, the xα2-peptide/Fyn-SH3 complex adopts a "sandwich"-like structure. In the membrane context, the xα2-peptide interacts with the Fyn-SH3 domain via the proline-rich region and the β-sheets of Fyn-SH3, with the latter wrapping around the proline-rich region in a form of a clip. These results provide a moredetailed glimpse into the context-dependent interaction dynamics and importance of the β-sheets in Fyn-SH3 and proline-rich region of MBP.3

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Turning White Matter “Inside-Out” by Hyper-deimination of Myelin Basic Protein (MBP)

Cited by 2 publications

References 301 publications

Interaction of Myelin Basic Protein with Myelin-like Lipid Monolayers at Air–Water Interface

Interaction of Myelin Basic Protein with Myelin-like Lipid Monolayers at Air–Water Interface

Docking and molecular dynamics simulations of the Fyn‐SH3 domain with free and phospholipid bilayer‐associated 18.5‐kDa myelin basic protein (MBP)—Insights into a noncanonical and fuzzy interaction

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