Membrane topology of PLP in CNS myelin: evaluation of models.
Three new models for proteolipid protein (PLP) topology in the myelin membrane have been proposed--the 4-helix N(in) and N(out) models of Popot (J. Membr. Biol. 120:233-246), and the model of Weimbs and Stoffel (Biochemistry 31:12289-12296). Unlike the earlier models proposed by Laursen (Proc. Natl. Acad. Sci. USA 81:2912-2916), Stoffel (Proc. Natl. Acad. Sci. USA. 81:5012-5016) and Hudson (J. Cell Biol. 109:717-727), the four hydrophobic clusters are all assigned as membrane-spanning domains. The Popot-N(in) and Weimbs models, which are similar to the Laursen model, both assign the positively-charged domain, which is deleted from the DM20 transcript of PLP, to the cytoplasmic surface, while the Popot-N(out) model, similar to the Stoffel and Hudson models, assigns this sequence to the extracellular surface. Our calculations of membrane surface charge shows that the disposition of this basic domain greatly influences membrane interactions, by shifting the equilibrium myelin period to alkaline pH due to the electrostatic repulsion force at the extracellular apposition. In the Laursen, Popot-N(in) and Weimbs models, the onset of swelling was calculated to be at lower pH than in the Stoffel, Hudson and Popot-N(out) models, and lower than that observed experimentally with mouse optic nerve myelin. The absolute electron density profile of the myelin membrane that is derived from the x-ray diffraction patterns shows similar density levels at its cytoplasmic and extracellular surfaces. By contrast, the electron density profile calculated from a chemical model that includes lipids plus myelin basic protein (but not PLP) shows a higher density at the cytoplasmic than at the extracellular side.(ABSTRACT TRUNCATED AT 250 WORDS)
Inouye
H
H
Children's Hospital, Boston, MA 02115.
Kirschner
D A
DA
D000818:Animals; D002490:Central Nervous System / Q000737:chemistry*; D004583:Electrons; D005069:Evaluation Studies as Topic; D006863:Hydrogen-Ion Concentration; D008565:Membrane Proteins / Q000737:chemistry*; D008956:Models, Chemical; D009185:Myelin Proteins / Q000737:chemistry*; D018991:Myelin Proteolipid Protein; D009186:Myelin Sheath / Q000737:chemistry*; D009994:Osmolar Concentration; D017434:Protein Structure, Tertiary
D008565:Membrane Proteins; D009185:Myelin Proteins; D018991:Myelin Proteolipid Protein