The figure below shows the orientation of a multipass transmembrane protein afte
ID: 56014 • Letter: T
Question
The figure below shows the orientation of a multipass transmembrane protein after it has completed its entry into the ER membrane (part A) and after it gets delivered to the plasma membrane (part B). This protein has an N-terminal signal sequence (depicted as the dark gray membrane-spanning box), which signal peptidase cleaves off in the endoplasmic reticulum. The other membrane-spanning domains in the protein are represented as open boxes. Given that any hydrophobic membrane-spanning domain can act as either a start-transfer region or a stop-transfer region, draw the final consequences of the actions described below on the orientation of the protein in the plasma membrane. Indicate on your drawing the extracellular space, the cytosolic face, and the plasma membrane, as well as the N- and C-termini of the protein.
A. [4pts] Deleting the first signal sequence
B. [4pts] Changing the hydrophobic amino acids in the first, cleaved, sequence to charged amino acids
C. [4pts] Changing the hydrophobic residues in every other transmembrane sequence to charged residues, starting with the first, cleaved, signal sequence
Explanation / Answer
A.
The signal sequence of a protein decides the location of a protein and its transportation from the cytosol to the target site. If the signal sequence was deleted, then the protein sequence exists in the cytosol of the cell.
B.
The signal sequence of a protein decides the location of a protein and its transportation from the cytosol to the target site. The protein that contains high amount of hydrophobic amino acids will be located in the transmembrane and hydrophilic amino acids are concentrated towards the cell interior and cell exterior. Hence, if the signal sequence was replaced with all hydrophilic amino acids then it exists in the cytosol of the cell leaving the remaining protein as transmembrane protein.
C.
The signal sequence of a protein decides the location of a protein and its transportation from the cytosol to the target site. The protein that contains high amount of hydrophobic amino acids will be located in the transmembrane and hydrophilic amino acids are concentrated towards the cell interior and cell exterior. Hence, if all the transmembrane sequences were replaced with hydrophilic amino acids instead of hydrophobic amino acids, then the entire protein with signal sequence exists in the cytosol of the cell.