Myelin‐specific proteins: A structurally diverse group of membrane‐interacting molecules

Abstract

The myelin sheath is a multilayered membrane in the nervous system, which has unique biochemical properties. Myelin carries a set of specific high-abundance proteins, the structure and function of which are still poorly understood. The proteins of the myelin sheath are involved in a number of neurological diseases, including autoimmune diseases and inherited neuropathies. In this review, we briefly discuss the structural properties and functions of selected myelin-specific proteins (P0, myelin oligodendrocyte glycoprotein, myelin-associated glycoprotein, myelin basic protein, myelin-associated oligodendrocytic basic protein, P2, proteolipid protein, peripheral myelin protein of 22 kDa, 2',3'-cyclic nucleotide 3'-phosphodiesterase, and periaxin); such properties include, for example, interactions with lipid bilayers and the presence of large intrinsically disordered regions in some myelin proteins. A detailed understanding of myelin protein structure and function at the molecular level will be required to fully grasp their physiological roles in the myelin sheath.

MOBP levels are regulated by Fyn kinase and affect the morphological differentiation of oligodendrocytes

“…It is therefore likely that the function of MOBP in respect to morphological differentiation is mediated by the N-terminal 68 amino acids present in all MOBP isoforms. This common N-terminus contains the above-mentioned cysteine-rich FYVE domain, a Zn 2+ -binding sequence postulated to mediate membrane binding by hydrophobic interactions, as well as binding of basic residues to negatively charged membrane lipids (Han et al, 2013). The C-termini of the larger MOBP isoforms do not seem to interact with membranes and have been proposed to be located in the small cytoplasmic space of the major dense line in compacted myelin (Myllykoski et al, 2012).…”

Dynamics of the Peripheral Membrane Protein P2 from Human Myelin Measured by Neutron Scattering—A Comparison between Wild-Type Protein and a Hinge Mutant

“…Myelin enables the rapid saltatory conduction of nerve impulses along axons, which can be up to a meter long in the PNS [1]. The myelin membrane contains 75–80% lipids by dry weight, with a high, 30–40%, cholesterol content [2], and it is enriched in myelin-specific proteins that are expressed by myelinating cells [3,4]. The myelin proteome has been under investigation for decades [5,6], but the structure and function of several myelin proteins are still poorly understood [3].…”

Neutron scattering studies on protein dynamics using the human myelin peripheral membrane protein P2

“…The role and function of myelin proteins remain poorly understood in both healthy myelin and as targets for several neurological diseases [1,2]. To understand myelin breakdown in pathology, it is of utmost importance to achieve a better knowledge of the parameters determining assembly and compaction of the myelin sheath [3].…”