title: Structural features of the extracellular portion of membrane-anchoring peptides on membrane-bound immunoglobulins.
abstract: Membrane-bound immunoglobulins, mIgs, are displayed as transmembrane proteins on the surface of B cells, where they serve as antigen receptors. The mIgs are anchored to the membrane through a carboxy-terminal extension of the immunoglobulin heavy chain. Three distinct structural regions of these membrane-anchor peptides, of mouse and human mIgs, have 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 intracytoplasmic; and (3) an N-terminal extracellular hydrophilic region of 13-67 amino acids, which is isotype-specific. Here we report predicted secondary and tertiary structures of the third structural region of the membrane anchoring peptide along with corroborating experimental evidence. The predictions of secondary and tertiary structure indicate that most of these regions can assume an chi-helical conformation. Circular dichroism spectroscopy of corresponding synthetic peptide confirms this essential feature. The choice of solvent and pH have dramatic effects on peptide helicity; solvent conditions consistent with a membrane-proximal environment promote helicity. Additional studies suggest that the two adjacent extracellular peptides may be stabilized through coiled-coil interactions similar to those described for some other transmembrane proteins.
authors.affiliation: Tanox Biosystems, Inc., Houston, TX 77025, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Major
authors.forename: F M
authors.initials: FM
authors.lastname: Davis
authors.forename: R S
authors.initials: RS
authors.lastname: Liou
authors.forename: T W
authors.initials: TW
authors.lastname: Chang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D005110:Extracellular Space / Q000276:immunology; D006801:Humans; D007132:Immunoglobulin Isotypes / Q000737:chemistry / Q000235:genetics; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D017433:Protein Structure, Secondary; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry* / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: D007132:Immunoglobulin Isotypes; D010455:Peptides; D011947:Receptors, Antigen, B-Cell