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 endosomal protein sorting 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 function 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 spectroscopic methods. The peptide was observed to exist in a mostly random structural state in aqueous solution but underwent high affinity association with dodecylphosphocholine micelles, where it adopted an ordered structure. The affinity of this peptide for the micellar surface and the structure of the bound peptide were independent of pH variation, surface charge, or attachment of a myristoyl anchor to the N-terminal. Studies with phospholipid vesicles suggested that the micellar structural 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 amphipathic helices, while 76-HPQY is non-helical and dimples just above the surface. These results contribute to the development of an understanding of the basis for specificity in recognition of sorting motifs by components of the cellular protein trafficking machinery.
Vinogradova
O
O
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio 44106-4970, USA.
Carlin
C
C
Sonnichsen
F D
FD
Sanders
C R
CR
D017503:Adenovirus E3 Proteins / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism; D002942:Circular Dichroism; D003600:Cytosol / Q000378:metabolism; D015536:Down-Regulation; D004705:Endocytosis; D066246:ErbB Receptors / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008823:Micelles; D008969:Molecular Sequence Data; D011487:Protein Conformation
D017503:Adenovirus E3 Proteins; C113428:E3-13.7 protein, human adenovirus; D008565:Membrane Proteins; D008823:Micelles; D066246:ErbB Receptors