Myelin structural proteins

Over 20 infectious agents have been incriminated as etiologic agents for many the causal relationship has been disproved, and for others there is conflicting evidence. Human herpesvirus 6 (HHV-6) is currently the most likely causative virus. HHV-6 may initiate the autoimmune processes of MS in one of two ways. First, HHV-6 is structurally similar to myelin basic protein. When T cells become sensitive to HHV-6, the cells may attack myelin basic protein. Second, HHV-6 may directly stimulate the complement cascade, activating autoimmune processes.5 Infection with HHV-6 alone cannot fully explain MS, because HHV-6 is found in 75% of all people, but MS is much more rare. 

Information concerning myelin structure is also available from electron microscope studies, which visualize myelin as a series of alternating dark and less dark lines (protein layers) separated by unstained zones (the lipid hydrocarbon chains) (Figs 4-4 to 4-7). There is asymmetry in the staining of the protein layers. The less dark, or intraperiod, line represents the closely apposed outer protein... 

Myelin basic protein. In PNS myelin, MBP varies from approximately 5% to 18% of total protein, in contrast to the CNS, where it is close to 30% [ 1 ]. In rodents, the same four 21,18.5,17 and 14kDa MBPs found in the CNS are present in the PNS. In adult rodents, the 14kDa MBP is the most prominent component and is termed Pr in the PNS nomenclature. The 18.5 kDa component is present and is often referred to as the P, protein in the nomenclature of peripheral myelin proteins. Another species-specific variation in human PNS is that the major basic protein is not the 18.5 kDa isoform that is most prominent in the CNS but rather a form of about 17 kDa. It appears that MBP does not play as critical a role in myelin structure in the PNS as it does in the CNS. For example, the shiverer mutant mouse, which expresses no MBP (Table 4-2), has a greatly reduced amount of CNS myelin, with no compaction of the major dense line. By contrast, shiverer PNS has essentially normal myelin,both in amount and structure, despite the absence of MBP. This CNS/PNS difference in the role of MBP is probably because the cytoplasmic domain of P0 has an important role in stabilizing the major dense line of PNS myelin. Animals doubly deficient for P0 and MBP have a more severe defect in compaction of the PNS major dense line than P0-null mice, which indicates that both proteins contribute to compaction of the cytoplasmic surfaces in PNS myelin [23],... 

Filbin, M. T. and Tennekoon, G. I. Myelin P0-protein, more than just a structural protein Bioessays 14 541-546,1992. 

Shapiro, L., Doyle, J. P., Hensley, P., Colman, D. R. and Hendrickson, W. A. Crystal structure of the extracellular domain from P0, the major structural protein of peripheral nerve myelin. Neuron 17 435-449,1996. 

Pelizaeus-Merzbacher disease (classical and connatal forms) and spastic paraplegia X-linked PLP Variable hypomyelination due to different mutations in the major structural protein of CNS myelin similar to rodent mutants such as the jimpy mouse 1,23... 

Because ALBP is related to several proteins of known structure, molecular replacement is an attractive option for phasing. The choice of a phasing model is simple here just pick the one with the amino-acid sequence most similar to ALBP, which is myelin P2 protein. Solution of rotation and translation functions refers to the search for orientation and position of the phasing model (P2) in the unit cell of ALBP. The subsequent paper provides more details. 

Molecular Replacement. The tertiary structure of crystalline ALBP was solved by using the molecular replacement method incorporated into the XPLOR computer program (Brunger et al., 1987). The refined crystal structure of myelin P2 protein without solvent and fatty acid was used as the probe structure throughout the molecular replacement studies. We are indebted to Dr. A. Jones and his colleagues for permission to use their refined P2 coordinates before publication. 

The initial model of ALBP was built by simply putting the amino acid sequence of ALBP into the molecular structure of myelin P2 protein. After a 20-step rigid-body refinement of the positions and orientations of the molecule, crystallographic refinement... 

Increased production of metabolites of phenylalanine that inhibit synthesis of a variety of substances required for normal brain growth Inhibition of TV-methyl-D-aspartate receptors, which are involved in memory and learning Competitive inhibition of transport of other amino acids required for protein synthesis Impaired polyribosome formation or stabilization Reduced synthesis/increased degradation of myelin Decreased formation of norepinephrine and serotonin Altered myelin structure and function... 

Cholesterol and membrane proteins, including structural ones such as glycophorin and myelin basic protein and functional ones such as -ATPase, bacteriorhodopsin, and cytochrome c, are important components of biological membranes. Cholesterol-lipid and a number of protein-lipid interactions have therefore been extensively investigated by vibrational spectroscopy. Interactions of hormones and toxins with phospholipid bilayers were also investigated. 

Roach A, Takahashi N, PravtchevaD, Ruddle F, Hood L 1985 Chromosomal mapping of mouse myelin basic protein gene and structure and transcription of the partially deleted gene in shiverer mutant mice. Cell 42 149-155... 

All three of these proteins are present in the lung. The lamellar bodies are secreted into alveolar lumen where they are transformed into an extracellular form of surfactant that has a quadratic lattice structure called tubular myelin. The three-dimensional tubulin-myelin structures spread in a monolayer at the air-liquid interface. This spreading decreases the surface tension, prevents alveolar collapse at the end of expiration, and confers mechanical stability to the alveoli. The surfactant system is in a continuous state of flux, and surfactant is recycled by uptake... 

Therefore, the importance of the conditions under which biological molecules are examined in the infrared needs to be emphasised. It is observed here, using the example of myelin basic protein, that this protein is very sensitive to the surroundings. The lipid environment more closely mimics the native environment, and thus presumably gives a far bettei indication of the native structure. 

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