Conformational studies of the beta-subunit of the high affinity IgE receptor: circular dichroism and molecular modelling.
The receptor with high affinity for immunoglobulin E (Fc epsilon RI) on mast cells and basophils plays an important role in mediating many of the pathophysiological phenomena associated with allergy. Fc epsilon RI is a tetrameric complex, alpha beta gamma2, of non-covalently attached subunits: one IgE-binding alpha-subunit with the binding site in the extracellular part of the chain, one beta-subunit and a dimer of disulphide linked gamma-subunits. In the present work, prediction of the three-dimensional structure of the four membrane-spanning segments of the beta-subunit has been achieved using rules of helix-helix packing arrangements and molecular dynamics calculations. It yielded a four-helix bundle with specific Van der Waals interactions between the helices. This four-helix bundle was used as a framework upon which to calculate the conformation of the beta-subunit excluding the C and N terminal cytoplasmic tails, but including the three chains that connect the four helices in the bundle. Separately, these synthetic 11, 17 and 29 residue bridge peptides were examined by circular dichroism (CD) spectroscopy and a degree of alpha-helical content in these bridge peptides was found. Additional molecular modelling of the bridge peptides indicate the central residues of these as the location of the helical moieties. Finally, in the model proposed for the beta-subunit, for each pair of consecutive transmembrane (TM) helices and its bridge peptide, a helix-loop-helix-loop-helix motif was found.
Zloh
M
M
University-Industry Centre for Pharmaceutical Research, School of Pharmacy, University of London, U.K.
Biekofsky
R R
RR
Duret
J A
JA
Danton
M
M
Gibbons
W A
WA
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D003198:Computer Simulation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D017455:Receptors, IgE / Q000737:chemistry*
D010446:Peptide Fragments; D017455:Receptors, IgE