Myelin P0-glycoprotein: predicted structure and interactions of extracellular domain.
Protein zero (P0), a transmembrane glycoprotein, accounts for over 50% of the total protein in PNS myelin. The extracellular domain of P0 (P0-ED) is similar to the immunoglobulin variable domain, carrying one acceptor sequence for N-linked glycosylation. The x-ray diffraction analysis of PNS myelin has demonstrated reversible transitions that depend on pH and ionic strength, resulting in three distinct structures characterized by widths of about 36 A, 50 A (native), and 90 A between the extracellular surfaces of the membranes. In the current work, we considered the constraints imposed by these x-ray diffraction data on the orientation of P0-ED, and we propose how this immunoglobulin-like domain could be accommodated in the variable widths of the extracellular space between myelin membranes. The modeling made use of the finding that beta-strand predictions for P0-ED are virtually superimposable with those of the VH domain of the phosphocholine-binding immunoglobulin M603 of mouse, which has a similar number of residues as P0-ED and a structure that has been solved crystallographically. The dimensions of P0-ED from the space-filling model, developed using PC-based molecular modeling software, were found to be 44 A x 25 A x 23 A. On the assumption that neither the shape nor the orientation of P0-ED changes appreciably, then the different widths at the extracellular apposition would easily accommodate P0-ED from apposed membranes if the molecules were oriented so that the beta-strands were approximately perpendicular to the membrane surface.(ABSTRACT TRUNCATED AT 250 WORDS)
Wells
C A
CA
Laboratory for the Study of Skeletal Disorders, Children's Hospital, Boston, Massachusetts 02115.
Saavedra
R A
RA
Inouye
H
H
Kirschner
D A
DA
D000595:Amino Acid Sequence; D000818:Animals; D002240:Carbohydrate Sequence; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018993:Myelin P0 Protein; D009185:Myelin Proteins / Q000737:chemistry* / Q000378:metabolism*; D009186:Myelin Sheath / Q000737:chemistry; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012584:Sciatic Nerve / Q000737:chemistry; D014961:X-Ray Diffraction
D015816:Cell Adhesion Molecules, Neuronal; D018993:Myelin P0 Protein; D009185:Myelin Proteins