An integral membrane protein, with large extracellular and cytoplasmic domains, spans the plasma membrane only once. When it initially synthesized, it is targeted to the ER co-translationally and contains a signal sequence and a stop transfer sequence. The signal sequence is cleaved by the signal peptidase. N-linked glycosylation occurs on an Asparagine residue located within the first half of the protein, prior to the stop transfer sequence. An asparagine after the stop transfer sequence is not modified. Which orientation must the protein be initially inserted in the ER membrane?

AThe N-terminus of the protein must be cytoplasmic

BThe protein must span the membrane twice with both the N and C termini in the cytoplasm

CIt can’t possibly be determined and I am willing to wager my entire grade in this course on this fact.

DOMG- Dr. Carr-Schmid better go over this in class because I have no clue this question is even asking!

ENone of the Above

Deletion of the ER signal sequence from the gene of a lysosomal protein would likely result in which of the following upon its synthesis?

ATransport to Nucleus

BCytosolic localization

CRetention in the ER


ELocalization in the lysosome

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