Heads or tails — what determines the orientation of proteins in the membrane

The same translocation machinery in the endoplasmic reticulum translocates either the N‐ or the C‐terminal domain of signal‐anchor proteins across the membranes. Charged residues flanking the signal sequence are important to determine which end is translocated, but are not sufficient to generate a uniform topology. The folding state of the N‐terminal segment, which is to be translocated posttranslationally, and the length or hydrophobicity of the signal sequence are additional criteria to determine protein orientation in the membrane.

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