title: High-resolution structural model of porcine P2 myelin membrane protein with associated fatty acid ligand: fact or artifact?
abstract: Myelin membrane is a biological complex of glial cells origin; it is composed of 25% (w/w) proteins and 75% lipids, and more than 300 proteins are associated with central nervous system myelin (for peripheral nervous system myelin, such data are lacking). Myelin plays an important role in maintaining propagation of nerve signals. To uncover the nature of propagation phenomena, it is essential to study biochemistry of myelin proteins and lipids, myelin composition, and myelin structure. Nearly all myelin proteins are like antigens, causing clinically well-defined devastating diseases; multiple sclerosis and Guillain-Barré syndrome are two of them. In this article, a high-resolution study (1.8 Å) of porcine myelin P2 protein is presented. Myelin was purified from porcine intradural spinal roots, which were stored at -80°C for 10 years before myelin and P2 protein were purified (spinal roots were a gift of Prof. Kunio Kitamura, Saitama Medical School). The three-dimensional structural analysis uncovered embedded 18-carbons-long fatty acid. Some speculative interpretation is presented, to uncover how this ligand of fatty acid may form cholesterol ester and stabilize the myelin structure or form simple raft microdomain. Protein crystallography indicates that the ligand may be 18-carbons-long fatty acid. This is unlike previous work with mass spectrometry, in which three ligands were determined. In other protein crystallography-based studies of P2 (bovine), an oleic fatty acid was suggested, but, for recombinant (human) protein, palmitic acid was found. There is no fatty acid ligand in equine P2 protein.
authors.affiliation: Department of Chemical Engineering and Technology, Protein Crystallization Facility KTH, Royal Institute of Technology, Stockholm, Sweden. sedzik@kth.se
authors.forename: Jan
authors.initials: J
authors.lastname: Sedzik
authors.forename: Jan Pawel
authors.initials: JP
authors.lastname: Jastrzebski
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray / Q000379:methods; D005227:Fatty Acids / Q000378:metabolism*; D008024:Ligands; D013058:Mass Spectrometry; D008956:Models, Chemical; D008970:Molecular Weight; D018993:Myelin P0 Protein / Q000737:chemistry* / Q000648:ultrastructure*; D009186:Myelin Sheath / Q000737:chemistry* / Q000648:ultrastructure; D011485:Protein Binding; D011487:Protein Conformation; D040901:Proteomics; D013126:Spinal Nerve Roots / Q000378:metabolism; D013552:Swine
chemical_list: D005227:Fatty Acids; D008024:Ligands; D018993:Myelin P0 Protein