A MEMBRANE SETTING FOR THE SORTING MOTIFS PRESENT IN THE ADENOVIRUS E3-13.7 PROTEIN WHICH DOWN-REGULATES THE EPIDERMAL GROWTH-FACTOR RECEPTOR

The adenovirus E3-13.7 protein interferes with endo somal protein sort ing to down-regulate the epidermal growth factor receptor and related tyrosine kinase receptors. The cytoplasmic C terminus of this protein contains three protein sorting motifs which are related to the functio n of E3-13.7, In this study, the structure of a 23-residue polypeptide corresponding to this domain was examined using solution NMR and CD s pectroscopic methods. The peptide was observed to exist in a mostly ra ndom structural state in aqueous solution but underwent high affinity association with dodecylphosphocholine micelles, where it adopted an o rdered structure. The affinity of this peptide for the micellar surfac e and the structure of the bound peptide were independent of pH variat ion, surface charge, or attachment of a myristoyl anchor to the N-term inal. Studies with phospholipid vesicles suggested that the micellar s tructural results can be extrapolated to a true lipid bilayer. On the micellar surface all three sorting motifs are closely associated with the water/apolar interface: 72-YLRH and 87-LL lie within interfacial a mphipathic helices, while 76-HPQY is non-helical and dimples just abov e the surface. These results contribute to the development of an under standing of the basis for specificity in recognition of sorting motifs by components of the cellular protein trafficking machinery.