Possible Hydrophobic Region in Myelin Basic Protein Consisting of an Orthogonally Packed β‐Sheet

Abstract

Theoretical analysis was carried out to determine how the ∼20% of β-structure observed in the 18.5 kilodalton (kDa) myelin basic protein (MBP) could be organized into a relatively stable β-sheet. The β-sheet is presumed to consist of the five most hydrophobic segments of polypeptide chain, which have β-structure potential. These correspond approximately to sequences 15–21, 37–45, 84–92, 106–112, and 148–154 (rabbit MBP sequence numbering) and constitute β-strands a,b,c,d, and e, respectively. A number of constraints are imposed upon the sheet; e.g., it should have the same topology in all MBP forms (21.5, 18.5, 17, and 14 kDa); strande should lie at the sheet edge; strands b, c, and d should be ordered sequentially; the sheet formed by strands a, b, c, and d should be antiparallel; a maximum of the nonpolar surface area should be removed from the aqueous milieu; and charged side chains should be solvent-accessible. On the basis of these constraints it is possible to propose six orthogonally packed β-sheets having different topologies. If strand e is restricted to an antiparallel alignment, the number of different sheets is reduced to four. Each of these sheets can form a relatively compact hydrophobic globular region. Two of the strands (a and e) can undergo transitions to α-helix without disrupting the structure of the remaining sheet bcd or producing major topologic rearrangements of the polypeptide chain.