FC0033
Myelin basic protein (MBP)  -  Actin

Biological function
The myelin basic protein (MBP) is part of the mammalian central nervous system that plays a role in maintaining the stability and integrity of the myelin sheath. Myelin signaling is achieved via direct interactions with a variety of molecules, such as calmodulin, actin and tubulin.

Domain organization/sequence features
The proline-rich segment of the membrane bound MBP interacts with diverse SH3 domain-containing ligands (e.g. Yes1, PSD95, cortactin, PexD, Abl, Fyn, c-Src, Itk).

Structural evidence
Solid-state NMR spectroscopy revealed that MBP in MBP-actin assemblies is structurally heterogeneous but gains ordered secondary structure elements (both α-helical and β-sheet), particularly in the terminal fragments and in a central immunodominant epitope.

Structure/Mechanism
In addition to the direct contacts with the proline residues, formation of all SH3 domain complexes is facilitated by long-range electrostatic interactions between the ID regions of MBP outside the binding context.

Mechanism category
competitive binding

Posttranslational modification
Phosphorylation, together with alternative splicing serves like a barcode for different signaling pathways

Significance
The interactions in combination with post-translational modifications and alternative splicing contribute to multifunctionality of MBP, and enable to integrate diverse signals from a variety of signaling pathways. The overall conformational polymorphism of MBP is consistent with its in vivo roles as both a linker (membranes and cytoskeleton) and a putative signaling hub.