Myelin P2 protein

Rostami, A., Gregorian, S. K., Brown, M. J. and Pleasure, D. E. Induction of severe experimental autoimmune neuritis with a synthetic peptide corresponding to the 53-78 amino acid sequence of the myelin P2 protein. J. Neuroimmunol. 30 145-151,1990. 

Baron P, Constantin G, D Andrea A, Ponzin D, et al. 1993. production of TNF and other proin-flammatory cytokines by human mononuclear phagocytes stimulated with myelin P2 protein. Proc Natl Acad Sd USA. 90 4414 1418. 

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... 

The adipocyte member of this family was named lipid-binding protein because it was found to bind both long-chain fatty acids and retinoic acid (Matarese and Bernlohr, 1988). It is also called adipocyte P2 (Hunt et al., 1986) because of its high sequence similarity to the Ixjvine myelin P2 protein (67%). The protein was suggested to play a role... 

P2 protein. PNS myelin contains a positively charged protein different from MBP that is referred to as P2 (Mr — 15,000). It is unrelated in sequence to MBP and is a member of a family of cytoplasmic fatty acid binding proteins (FABP) that are present in a variety of cell types [25]. The amount of P2 protein is variable among species, accounting for about 15% of total protein in bovine PNS myelin, 5% in humans and less than 1% in rodents. P2 protein is generally considered a PNS myelin protein but it is expressed in small amounts in CNS myelin sheaths of some species. P2 is an antigen for experimental allergic neuritis, the PNS counterpart of EAE (see Chs 36 and 38). P2 appears to be present in the major dense line of myelin sheaths, where it may play a structural role similar to MBP... 

Fig. 4-11). Interestingly, the larger amounts of P2 protein that are in myelin of some species correlate with increased widths of the major dense lines as determined by X-ray diffraction, and there appears to be substantially more P2 in large sheaths than small ones [4]. The large variation in the amount and distribution of the protein from species to species and sheath to sheath raises so far unanswered questions about its function. Its similarities to cytoplasmic proteins in other cells, whose functions appear to involve solubilization and transport of fatty acids and retinoids, suggest that it might function similarly in myelin assembly or turnover, but there is currently no direct experimental evidence to support this hypothesis. 

Martenson, R. and Uyemura, K. Myelin P2, a neuritogenic member of the family of cytoplasmic lipid binding proteins. In R. E. Martenson (ed.), Myelin biology and chemistry. Boca Raton, FL CRC Press, 1992, pp. 509-530. 

Note that the myelin P2 coordinates were not yet available from the Protein Data Bank and were obtained directly from the laboratory in which the P2 structure was determined. Because of the time required for publication of research papers and processing of coordinates by the PDB, coordinates may be available directly from a crystallographic research group several months before they are available from PDB. 

Myelin P2 was the first protein in the iLBP family whose structure was determined (Jones et al., 1988). The crystals contain three copies of the molecule in the asymmetric unit and the structure has now been refined at 2.7 A (Cowan et al., 1993). Because the crystals do not diffract beyond 2.7 A, the precision of the model is not as high as in the other studies and this factor could affect precise hydrogen bonding measurements. In an attempt to overcome this problem, the three molecules were restrained to be similar during the refinement. Only well-determined water molecules were included in the final model. No fatty acid was added to the sample, but later mass spectroscopy measurements indicated that the predominant ligand was oleic acid, which also agreed with the shape of the electron density. This density could not be accounted for by the protein model. 

Last of all, it is noteworthy that myelin P2 is a basic protein. With added positively charged groups on its surface, it seems reasonable to assume that the side chains on the outside surface of the molecule are available to interact with phospholipid head groups in the myelin membrane. 

Nagai, Y., Uchida, T, Takeda, S., and Ikuta, F., 1978, Restoration of activity for induction of experimental allergic peripheral neuritis by a combination of myelin basic protein P2 and gangliosides from peripheral nerve, Neurosci. Lett. 8 247-254. 

There is a second family of small lipid-binding proteins, the P2 family, which include among others cellular retinol- and fatty acid-binding proteins as well as a protein, P2, from myelin in the peripheral nervous system. However, members of this second family have ten antiparallel p strands in their barrels compared with the eight strands found in the barrels of the RBP superfamily. Members of the P2 family show no amino acid sequence homology to members of the RBP superfamily. Nevertheless, their three-dimensional structures have similar architecture and topology, being up-and-down P barrels. 

Basic protein P2 has a molecular weight of 15 kDa and is a member of a family of cytoplasmic lipid-binding proteins. Unlike other myelin proteins, its quantitative expression varies greatly according to species, ranging from less than 1% in rodent sciatic nerves up to 5-14% in human, bovine, and rabbit nerve. P2 is located on the cytoplasmic side of compacted regions of myelin. 

P2 P2, a basic protein with a molecular weight about 13.5kDa, is located on the cytoplasmic side of the compact myelin membranes. It may serve as lipid carrier and thus could be involved in the assembly, remodeling and maintenance of myelin (Garbay et al., 2000). 

P2 is a component of myelin from the peripheral nervous system. It is localized on the cytoplasmic side of Schwann cells where it behaves as peripheral membrane protein, although a small amount is found in the cytoplasm (Trapp et al., 1984). Like the other iLBPs, the exact biochemical role of P2 is unknown. Its cellular localization and its ability to bind different fatty acids and retinoids (Uyemura et al., 1984) suggest that it may function in fatty acid trafficking. It would therefore play a major role in the movement of fatty acids between the site of uptake and that of esterification during the massive phospholipid synthesis phase of myelinating Schwann cells. 

Cowan, S. W., Newcomer, M, E., and Jones, T. A. (1993) Crystallographic studies on a family of cellular lipophilic transport proteins-refinement of P2 myelin... 

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