High resolution structures of myelin proteins

• Research unit: EU RFP
• Project number: 96.0145-1

Key words (English)

Basic myelin protein; Cubic phase crystallization; High resolution; Proteolipid; Structure

Alternative project number (English)

EU project number: BMH4CT960990

Research programs (English)

EU-programme: 4. Frame Research Programme - 4.2 Agriculture and agroindustry

Short description (English)

See abstract

Partners and International Organizations (English)

Ourisson, G. et al.

Abstract (English)

Crystallization of myelin proteins PLP and MBP

PLP is the protein moiety in the membrane of the myelin sheath, and MBP is thought to be associated peripherally. The proteolipids are most complicated, being heterodisperse and palmitoylated, and the biochemistry underlying the crystallization studies. is complex. Knowledge of the structures of the myelin proteins is essential for understanding the degenerative diseases in which they participate, most notably multiple sclerosis . We have initiated a project of devising a novel crystallization methodology for membrane proteins using lipidic mesophases, and have succeeded in adapting lipidic cubic phases to mimic the rheology of the membrane as crystallization matrices. The phase behavior was studied by means of freeze-fracture and ultrathin sections of materials by electron microscopy, as well as frozen-hydrated samples. Small-angle X-ray scattering is probably the most powerful method. Detailed determinations of the effects of additives on the phases were studied by in-house facilities and at the synchrotron. Lateral pressure determinations of bilayers of various characteristics were initiated by fluorescence quenching measurments using the excimer formation of pyrene. The results of these studies will affect the development of structural investigations of membrane protein in general. In particular, this approach has been successfully applied to small molecules, soluble proteins (lysozyme) and membrane proteins- bacteriorhodopsin and two photosynthetic reaction centers. The first high resolution X-ray structure of bacteriorhodopsin was elucidated, explaining the mechanism of proton translocation of this light-induced proton pump, and the crystals were found to undergo the native photocycle. We are optimistic that similar approaches using lipidic mesophases will eventually yield crystals of some of the myelin proteins.

References in databases (English)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 96.0145-1