Final answer:
The orientation of membrane proteins during synthesis is guided by the translocon in the RER, with certain signal sequences dictating the positioning of the protein's ends. The correct statement is that during synthesis, the translocon usually orients the polypeptide so the more positive end faces the cytosol.
Step-by-step explanation:
The orientation of membrane proteins in the membrane is typically accomplished during synthesis. As a nascent polypeptide emerges during translation, it interacts with the translocon in the rough endoplasmic reticulum (RER). Specific sequences in the polypeptide, such as N-terminal signal sequences and stop-transfer sequences, guide insertion and orientation. For a protein that crosses the membrane multiple times, these sequences dictate the locations of its N- and C-termini, with the N-terminal end commonly exposed to the outside of the cell.
The more hydrophobic alpha helical domains anchor the protein in the membrane. Therefore, statement 2 is the most accurate: 'During synthesis, the translocon inner lining usually orients the nascent polypeptide so the more positive end faces the cytosol'.