Disease relevance of PMP2

• There is now overwhelming evidence that P2 protein is the crucial antigen involved in the induction of experimental allergic neuritis, an autoimmune disease of the peripheral nervous system [1].
• The complete amino acid sequence of rabbit P2 protein was derived by sequence analysis of cyanogen bromide peptides and peptides obtained by proteolysis using Staphylococcus aureus V8 enzyme, trypsin, or clostripain [1].
• The sequences encoding human and fungal P2 protein were subcloned, expressed in Escherichia coli as His6-tagged fusion proteins, and purified by Ni2+-chelate affinity chromatography [2].
• This antibody passively protected infant rats against type b Haemophilus infection caused by the homologous organism, but not against challenge by a strain with the heterologous 36,500 mol wt P2 protein [3].
• The P2 sequence (YVNVNMGLK) purified from liver tissue was in concordance with that encoded by the viral genome for the HBV nucleocapsid antigen or HBcAg 88-96 [4].

High impact information on PMP2

• The allergen, formally termed rAsp f 8, shares >62% sequence identity and >84% sequence homology to corresponding eukaryotic P2 proteins, including human P2 protein [2].
• To investigate the mechanisms of action of PMPs leading to membrane damage, we used flow cytometry to compare the effects of two distinct PMPs (thrombin-induced PMP-1 [tPMP-1] or PMP-2) with human neutrophil defensin-1 (hNP-1) on transmembrane potential (Deltapsi), membrane permeabilization, and killing of S. aureus [5].
• Collectively, these data indicate that membrane dysfunction and cell death due to tPMP-1, PMP-2, or hNP-1 likely involve different mechanisms [5].
• Growth in menadione reconstituted Deltapsi of JB-1 to a level equivalent to 6850, and was associated with greater depolarization due to PMP-2, but not tPMP-1 [5].
• P2 peptide could also be isolated from the EBV-transformed B cells that were transfected by HBcAg-expressing vector [4].

Chemical compound and disease context of PMP2

• Two myelin proteins, P2 basic protein and P0 glycoprotein, can induce experimental autoimmune neuritis (EAN), a model of human inflammatory neuropathy [6].
• Using polyacrylamide gel electrophoresis, the viral proteins were identified as derived from the P1 (5' terminal), P2 (middle), or P3 (3' terminal) region of the poliovirus translation unit [7].
• When injected i.p. into histocompatible Lewis or F1 (Lewis X P2) recipients, the BP-1 line induced both clinical signs of experimental autoimmune encephalomyelitis (EAE) and delayed type hypersensitivity (DTH) reactions in ears challenged intradermally with GP-BP but not PPD [8].
• In the case of BH10-LD3, these four mutations were MA1, CA1, MP2, and MNC, and they involved changes of amino acid Val-35 to Ile within the matrix protein (MA), Ile-91 to Thr within the capsid (CA), Thr-12 to Ile within p2, and Thr-24 to Ile within the nucleocapsid (NC) [9].
• Compared to the lower resolution NMR structure for the homologous protein P2 from the Pseudomonas sp. CF600 phenol hydroxylase system (RMSD = 2.48 A for backbone atoms) (Qian, H., Edlund, U., Powlowski, J., Shingler, V., and Sethson, I. (1997) Biochemistry, 36, 495-504), that of MMOB reveals a considerably more compact protein [10].

Biological context of PMP2

• The gene for human PMP2 was assigned to chromosome 8q21.3-q22.1 by spot hybridization of flow-sorted human chromosomes and fluorescence in situ hybridization [11].
• Peripheral myelin protein 2 (PMP2) is a small, basic, and cytoplasmic lipid binding protein of peripheral myelin [11].
• Exonic SNPs at positions 220 (A/G) and 445 (C/T) of the peripheral myelin protein 2 (PMP2) [12].
• The complete amino acid sequence of human P2 protein [13].
• We describe the application of single-strand conformation polymorphism (SSCP) analysis to the speciation of human microsporidia after polymerase chain reaction (PCR) amplification with the panmicrosporidian primers PMP1 and PMP2 [14].

Anatomical context of PMP2

• The myelin P2 protein, a 14,800-Da cytosolic protein found primarily in peripheral nerves, belongs to a family of fatty acid binding proteins [15].
• By using a panel of human-hamster somatic cell hybrids and by in situ hybridization, we have mapped the human P2 gene to segment q21 on the long arm of chromosome 8 [15].
• Gas3/PMP2 accumulates within late endosomes close to the juxtanuclear region, whereas in the proximity of the cell periphery, it induces the formation of actin/phosphatidylinositol (4,5)-bisphosphate (PIP(2))-positive large vacuoles [16].
• The three-dimensional structure of P2 protein from peripheral nervous system myelin has been determined at 2.7 A resolution by X-ray crystallography [17].
• Myelin P2 is a 14,800-Da cytosolic protein found in rabbit sciatic nerves [18].

Associations of PMP2 with chemical compounds

• The complete amino acid sequence of P2 protein from human peripheral nerve myelin was determined from nine staphylococcal protease peptides and four cyanogen bromide peptides [13].
• Several generalized dissociation pathways were proposed and were evaluated theoretically with truncated leucine-containing models using ab initio calculations at B3-PMP2/6-311 ++ G(3df,2p)//B3LYP/6-31 ++ G(d,p) level [19].
• Product analysis, isotope labeling ((2)H and (18)O), and potential energy surface mapping by ab initio calculations at the G2(MP2) and B3-PMP2 levels of theory and in combination with Rice-Ramsperger-Kassel-Marcus (RRKM) kinetic calculations are used to assign the major and some minor pathways for 1 dissociations [20].
• In the present study the ionization energy thresholds (IET's) of uracil and thymine have been calculated (with the B3LYP, PMP2, and P3 levels of theory using the standard 6-31++G(d,p) basis set) with one to three water molecules placed in the first hydration shell [21].
• The cysteine and selenocysteine oxidation by H2O2 in vacuo and in aqueous solution was studied using the integrated molecular orbital + molecular orbital (IMOMO) method combining the quadratic configuration method QCISD(T) and the spin projection of second-order perturbation theory PMP2 [22].

Other interactions of PMP2

• This result identifies the myelin P2 gene as a candidate gene for autosomal recessive Charcot-Marie-Tooth disease type 4A [15].
• Lymphocytes from patients with acute transverse myelopathy (ATM) were shown to undergo a specific and significant transformation when cultured in vitro in the presence of either the central nervous myelin basic encephalitogenic protein (BE) or the peripheral nerve myelin P2 protein [23].
• In addition, using SSCP and our physical map, we have demonstrated that the myelin protein PMP-2, mapped by FISH to this region, is not the defect in CMT4A [24].

Analytical, diagnostic and therapeutic context of PMP2

• Isolation and sequence determination of cDNA encoding P2 protein of human peripheral myelin [25].
• PCR was performed with primer pairs V1-PMP2, V1-EB450, and V1-SI500, and the nature of the PCR products was confirmed by Southern blot hybridization [26].
• Rabbit antibody prepared against P2 from one strain was cross-reactive with P2 isolated from the other two heterologous strains by Western blot [3].
• Here we demonstrate that i.v. administration of as little as 100 microg of recombinant P2 protein twice daily completely prevents experimental autoimmune neuritis induced by adoptive transfer of neuritogenic P2-specific T cells or by immunization with the neuritogenic P2-peptide-spanning amino acids 53-78 [27].
• P0, P1, and P2 were isolated as a macromolecular complex by preparative isoelectric focusing and anion-exchange chromatography in the presence of 6 M urea [28].

References