Adhesion and clustering of charge isomers of myelin basic protein at model myelin membranes

Myelin basic protein: a multifunctional protein

“…Phosphorylation of both C1 and C2 with rabbit muscle kinase decreased their ability to aggregate lipid vesicles [95] and also decreased their permeabilizing effect on vesicles, indicating decreased hydrophobic interactions with the bilayer [151]. Differential association of the charge isomers, which depended on protein concentration, with planar membranes has also been observed [152]. However, at higher MBP/lipid ratios similar to those found in compact myelin, all charge isomers except C8 aggregated large unilamellar vesicles (LUVs) containing phosphatidylcholine (PC) and 10-20% of a single negatively charged lipid such as phosphatidylserine (PS), to a similar degree [150].…”

A Tale of Two Citrullines—Structural and Functional Aspects of Myelin Basic Protein Deimination in Health and Disease

“…In addition, when myelin is fractionated by discontinuous sucrose gradient centrifugation, the highly deiminated C8 charge isomer was found in the loose myelin fractions that contained fewer lamellae; by comparison, the highly cationic C1 isomer was found in the compact myelin fractions with extensive multilamellae [215]. Other methodologies also indicate a diminished ability of deiminated MBP to interact with and compact lipids [174,193,198]. Thus, the reduction in net positive charge of MBP inhibits the protein's ability to maintain the tight compaction of the major dense line.…”

“…It has been suggested that the varied post-translational modifications target individual MBP variants to different intracellular locations [70], and a recent physicochemical study has shown how this localisation might occur [198]. Using optical waveguide lightmode spectrometry, Shanshiashvili et al [198] demonstrated that different charge components of bovine 18.5-kDa MBP interacted differently with model membranes in terms of their association rate coefficient, adhesion, conformation, and clustering tendency.…”

Assessment of Citrullinated Myelin by1H-MR Spectroscopy in Early-Onset Multiple Sclerosis

“…Thus, the interaction of MBP with lipids and its "glue activity" for adjacent bilayers are reduced. 11,12 In addition to such structural alterations, citrullinyl residues are associated with faster digestion of MBP by proteases. 4 The enzymes involved in deimination, peptidylarginine deiminases (PADs), have been found upregulated in MS due to hypomethylation of their promoter region.…”