User:Vazi97/sandbox

Structure
Myelin basic protein is a net-positive, membrane-associated, intrinsically disordered protein. It is basic, with an isoelectric point of 10, and is thought to associate with negatively charged phospholipid heads of the plasma membrane. Due to post-translational modifications, it can exist as various charge isomers known as C1-C6 or C8. C1-C6 each undergo ADP-ribosylation at Arg9 and Arg54; in addition, C1 is the least modified (and most positively charged), C2 is deamidated, and C3-C6 undergo a combination of phosphorylation, deamidation, and deimination. C8 is the most distinct, containing 6-11 citrullinations beyond C1, each of which decrease its positive charge and alter its ability to hydrogen bond. Additionally, they may undergo acylation of the N-terminal alanine, methylation of Arg107, and addition of an azido-GTP at Gln3.

Myelin basic protein has been classified as an intrinsically disordered protein that has no stable secondary structure in solution. Like most IDPs, it has a high net charge and a low mean hydrophobicity, minimizing the hydrophobic effect that drives traditional protein folding. It does contain some exceptions to normal IDP amino acid content. For example, MBP has more arginine and less glutamic acid than most IDPs. However, this is likely because those changes are necessary for MBP to be sufficiently basic and positively charged to correctly interact with the membrane. Notably, MBP has been shown to adopt a more stable secondary structure on interaction with lipids. Experiments have predicted this structure to contain beta sheet and regions of amphipathic helix.

References:

1.      Ahmed et al. “Induced Secondary Structure and Polymorphism in an Intrinsically

Disordered Structural Linker of the CNS: Solid-State NMR and FTIR

Spectroscopy of Myelin Basic Protein Bound to Actin.”

2.      Radivojac, P., L. M. Iakoucheva, C. J. Oldfield, Z. Obradovic, V. N.

Uversky, et al. 2007. Intrinsic disorder and functional proteomics.

Biophys. J. 92:1439–1456. (IDPs)

3.       Receveur-Brechot, V., J. M. Bourhis, V. N. Uversky, B. Canard, and S.

Longhi. 2006. Assessing protein disorder and induced folding. Proteins.

62:24–45. (IDPs)

4.       Boggs, J. M. 2006. Myelin basic protein: a multifunctional protein. Cell.

Mol. Life Sci. 63:1945–1961. (Review)

5.       Boggs, J. M., G. Rangaraj, W. Gao, and Y. M. Heng. 2006. Effect of

phosphorylation of myelin basic protein by MAPK on its interactions

with actin and actin binding to a lipid membrane in vitro. Biochemistry.

45:391–401.