TY - JOUR
T1 - Interaction of nascent preproparathyroid hormone molecules with microsomal membranes
AU - Baba, Hisamitsu
AU - Karaplis, Andrew C.
AU - Wiren, Kristine M.
AU - Keutmann, Henry T.
AU - Kronenberg, Henry M.
PY - 1992/2
Y1 - 1992/2
N2 - To characterize the early steps in the interaction of nascent chains of preproparathyroid hormone (prepro‐PTH) with the secretory apparatus, such truncated nascent chains still attached to ribosomes were tested for binding to microsomal membranes and cleavage by signal peptidase. Nascent chains of 114, 97, 88, 81, 70, and 59 residues were tested for their ability to bind tightly to membranes and to undergo signal sequence cleavage. Chains of 81 residues and longer bound tightly to the membranes and were cleaved by signal peptidase. The 88‐ and 81‐residue precursors and their corresponding pro‐proteins were less efficiently associated with the membranes than were the 114‐ and 97‐residue precursors and their corresponding pro‐proteins. The 70‐residue chain bound to the membrane but was not cleaved. When this peptide was subsequently released from the ribosome with puromycin, it was cleaved by signal peptidase. The 59‐residue chain bound only slightly to the microsomal membrane and was not cleaved by signal peptidase, even when the nascent peptide was released from the ribosome with puromycin. Thus the critical length for productive binding to microsomal membranes is between 59 and 70 residues; the length required for signal cleavage is between 70 and 81 residues.
AB - To characterize the early steps in the interaction of nascent chains of preproparathyroid hormone (prepro‐PTH) with the secretory apparatus, such truncated nascent chains still attached to ribosomes were tested for binding to microsomal membranes and cleavage by signal peptidase. Nascent chains of 114, 97, 88, 81, 70, and 59 residues were tested for their ability to bind tightly to membranes and to undergo signal sequence cleavage. Chains of 81 residues and longer bound tightly to the membranes and were cleaved by signal peptidase. The 88‐ and 81‐residue precursors and their corresponding pro‐proteins were less efficiently associated with the membranes than were the 114‐ and 97‐residue precursors and their corresponding pro‐proteins. The 70‐residue chain bound to the membrane but was not cleaved. When this peptide was subsequently released from the ribosome with puromycin, it was cleaved by signal peptidase. The 59‐residue chain bound only slightly to the microsomal membrane and was not cleaved by signal peptidase, even when the nascent peptide was released from the ribosome with puromycin. Thus the critical length for productive binding to microsomal membranes is between 59 and 70 residues; the length required for signal cleavage is between 70 and 81 residues.
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U2 - 10.1002/jbmr.5650070211
DO - 10.1002/jbmr.5650070211
M3 - Article
C2 - 1570764
AN - SCOPUS:0026557137
SN - 0884-0431
VL - 7
SP - 199
EP - 206
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 2
ER -