Consider a transmembrane protein with the following topology that has an internal signal sequence (helix 1). If you fuse a canonical ER signal sequence at the N-terminus of this protein, how would you expect the topology to change? The ER lumen is at the bottom in all drawings. For simplicity, assume that the effect of charged residues flanking the transmembrane helices is negligible in this case.

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Quizplus · Accepted Answer

Introducing the N-terminal signal sequence (which would be cleaved) converts helix 1 into a stop-transfer signal, orienting the entire protein inside-out. This is a simplification, however; for example, the effect of charged residues in the loop regions also requires consideration.

Consider a Transmembrane Protein with the Following Topology That Has