STRUCTURAL FEATURES OF THE EXTRACELLULAR PORTION OF MEMBRANE-ANCHORING PEPTIDES ON MEMBRANE-BOUND IMMUNOGLOBULINS

Membrane-bound immunoglobulins, mIgs, are displayed as transmembrane p roteins on the surface of B cells, where they serve as antigen recepto rs. The mIgs are anchored to the membrane through a carboxy-terminal e xtension of the immunoglobulin heavy chain. Three distinct structural regions of these membrane-anchor peptides, of mouse and human mIgs, ha ve been delineated: (1) a central conserved stretch of 25 hydrophobic, unchanged amino acid residues, which spans the membrane lipid bilayer ; (2) a C-terminal hydrophilic region of 3-28 amino acids; which is in tracytoplasmic; and (3) an N-terminal extracellular hydrophilic region of 13-67 amino acids, which is isotype-specific. Here we report predi cted secondary and tertiary structures of the third structural region of the membrane anchoring peptide along with corroborating experimenta l evidence. The predictions of secondary and tertiary structure indica te that most of these regions can assume an a-helical conformation. Ci rcular dichroism spectroscopy of corresponding synthetic peptides conf irms this essential feature. The choice of solvent and pH have dramati c effects on peptide helicity; solvent conditions consistent with a me mbrane-proximal environment promote helicity. Additional studies sugge st that the two adjacent extracellular peptides may be stabilized thro ugh coiled-coil interactions similar to those described for some other transmembrane proteins.