emerges from the ribosome and induces an immediate delay (answer b)in
translation until the ribosome interacts with a docking protein (answer d),
also known as an SRP receptor, in the ER membrane. In the function of the
RER, a presequence on the 3’-end of the AUG initiation codon is translated
as an N-(amino)-terminal presequence [amino-terminal signal leader
(prepeptide) sequence] that recognizes the ER membrane and leads to the
translocation of the peptide across the ER membrane. This recognition is
accomplished through the SRP, which cycles between the ER membrane
and the cytosol. After the SRP-bound ribosome attaches to the ER mem-
brane via the docking protein, translation continues with displacement of
the SRP for subsequent recycling and translocation of the peptide across
the ER membrane. Enzymatic cleavage (answer e)of the signal sequence
releases the newly synthesized peptide.
56.The answer is e.(Alberts, pp 355–357.)The patient in the scenario
suffers from Alzheimer disease which is related to protein misfolding lead-
ing to neurofibrillary tangles. Three-dimensional folding is required for
functional activity of proteins. Native folding of a protein is encoded in its
amino acid sequence; however, protein folding inside cells requires molec-
ular chaperones binding and releasing themselves from hydrophobic
regions of the newly synthesized protein and ATP to reach their native
folded state. Various chaperones protect nonnative protein chains from
misfolding and aggregation (answer a),but do not contribute conforma-
tional information to the folding process (answer b).Many chaperones are
also stress- or heat-shock proteins (HSPs) that stabilize preproteins for
membrane translocation, present misfolded proteins for proteolysis
(answer d),and regulate the conformation of signaling molecules. The
underlying principle in all these functions is the recognition by chaperones
of proteins in their nonnative states. Chaperones also inhibit the formation
of partially folded intermediates. Chaperones in conjunction with calretic-
ulin monitor the progress of folding and ensure that only properly folded
proteins are secreted from the cell or shipped to lysosomes. It is hypothe-
sized that this level of ER “quality control” is absent in Alzheimer and
other neurodegenerative diseases. Chaperones assist with translocation of
proteins across internal membranes (e.g., mitochondria) by maintaining
precursor proteins in their unfolded state during membrane trafficking.
They do notfunction in the docking of the signal peptide (answer c).
134 Anatomy, Histology, and Cell Biology