HEADS OR TAILS - WHAT DETERMINES THE ORIENTATION OF PROTEINS IN THE MEMBRANE

The same translocation machinery in the endoplasmic reticulum transloc ates either the N- or the C-terminal domain of signal-anchor proteins across the membranes, Charged residues flanking the signal sequence ar e important to determine which end is translocated, but are not suffic ient to generate a uniform topology. The folding state of the N-termin al segment, which is to be translocated posttranslationally, and the l ength or hydrophobicity of the signal sequence are additional criteria to determine protein orientation in the membrane.