User:Naironfire/sandbox

= Myelin Protein Zero =

Bibliography:
==== "Peripheral Neuropathies caused by mutations in the myelin protein zero" ==== Notes:

-gene that encodes MPZ located on chromosome 1 near Duffy Locus

-mutation in MPZ >causes demyelinating neuropathy also called Charcot-Marie Tooth Disease

-MPZ = major myelin protein expressed by Schwann Cells. =50% of all PNS proteins

-gene= divided into 6 exons distributed 7Kb of of DNA

-only expressed by myelinating schwann cells (not found in other tissues like CNS myelin)

-sequence 95% identical in rats, cows, and humans

-six exons ---> 248 amino acids but exon one part is cleaved off so new total- 219 amino acids

-1-124= extracellular domain 125-150= transmembrane  domain   151-219: cytoplasmic domain

-MPZ expression induced by (still) unknown axon signals

==== "Myelin Specific proteins: A structurally diverse group of membrane-interacting molecules" ==== Notes:

-Myelination: myelinating cell wraps its membrane around an axon multiple times

-MPZ located within compact myelin

-extracellular domain: has signal Ig domain

-cytoplasmic domain: very positively charged but does not fold in globular domain. has the tendency to form secondary structures

====  "Phenotypic Clustering in MPZ Mutations" ==== Notes:

-Member of the immunoglobin family has extracellular and transmembrane domains

homotypic interactions (interactions between two MPZ extracellular domains) keep myelin wraps adhered next to each other

-needed for myelin compaction ---> mutations lead to humans developing dysmyelinating neuropathy (CMT1B)

-some mutations cause neuropathy in infancy (Dejerine-Sottas disease) while others cause Charcot-Marie-Tooth within first two decades and others cause neuopathy in adulthood CMT2

-adding charged amino acid or changing cysteine residue can in domain can cause neuropathy onset early on. So can cutting short cytoplasmic domain or changing conserved amino acid.

-disrupting MPZ tertiary structure can result in neuropathy.

==== "Membrane Adhesion in Peripheral Myelin: Good and Bad Wraps with protein P0" ==== Notes:

-extracellular domain similar to immunoglobin domain

-without MPZ, hypomyelination and and degeneration of myelin

-membrane adhesion through interaction of lipids and tryptophans

-mutations in MPZ could result in impaired homophillic interactions (adhesion?)

==== "Packing of Myelin Protein Zero" ==== Notes:

-MPZ's ability to self adhere (adhere to other MPZs) is important for keeping myelin sheath layer together

-tetrameric folding

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"Isolation and Analysis of the Gene Encoding Peripheral Myelin Protein Zero"

-MPZ hypothesized as cell adhesion molecule

-MPZ extracellular domain is similar to immunoglobulin domain known to facilitate homotypic and heterotypic interactions in immune and nervous systems

-Not produced by CNS myleninating gilial cells or by Schwann cells that do not express Myelin

-Function: compaction of the myelin sheath does so at two positions

1) joining of cytoplasmic membrane faces

2) joining of extracellular membrane faces.

MPZ immunoglobin domain is similar to those of polyimmunoglobin and T4 protein which also function as binding and adhesion molecules which also interact with similar immunoglobin molecules so extracellular domain of MPZ interacts with itself than with lipids or other stuff in membrane

Only member of immunoglobin family to have just one domain

"Neuroactive Steroids and Peripheral Myelin Proteins"

-MPZ is a single membrane glycoprotein, a protein with carbohydrate groups attached to its polypeptide chain. Single transmembrane with cytoplasmic and extracellular domains (crosses membrane once)

"Crystal Structure of the Extracellular Domain from P0, the Major Structural Protein of Peripheral Nerve Myelin"

-MPZ has highly basic amino acid residues

-69 intracellular domain  124 residue extracellular domain

-membrane apposition done by intracellular domain which may interact with lipid headgroups through electrostatic interactions

-In the extracellular space, membrane juxtaposition done by homophilllic interactions of P0 extracellular domain

-through homophillic adhesion in extracellular domain adjacent membrane wraps are held togther

structure:

10 beta strands arranged as two beta sheets

-hydrophobic core like other immunoglobin domain proteins

-strands DEBA make up one sheet A'GFCC'C '' make up other sheet

-MPZ molecules from tetramers

-bind to membrane either with homophillic protein -protein interactions or with extracellular tryptophan interacting with membrane

-Myelination derived from signal from axons

"Myelin Protein Zero Exists as Dimers and Tetramers"

-Myelin can form tetramers and dimers