New variation on the translocation of proteins during early biogenesis of apolipoprotein B.
Apolipoprotein B (apo B) is crucial for the transport of cholesterol in humans. It is a large secretory protein that mediates the uptake of low-density lipoproteins and renders several forms of lipid droplets soluble in the blood. The binding of lipid by apo B also prevents this hydrophobic protein from precipitating in aqueous solution. In the endoplasmic reticulum, nascent secretory proteins must be translocated through an aqueous channel in the membrane into the aqueous lumen, so some novel form of processing may be necessary to maintain the solubility of apo B during its translocation. We have discovered that the biogenesis of apo B in cell-free systems does indeed involve a new variation on protein translocation: unlike typical secretory proteins, apo B is synthesized as a series of transmembrane chains with large cytoplasmic domains and progressively longer amino-terminal regions that are protected against added proteases during the translocation process. In contrast to typical transmembrane proteins, these transmembrane chains are not integrated into the bilayer. Moreover, the transmembrane chains with the shortest protected domains are precursors of forms whose protection is progressively extended to cover the length of the protein. This stepwise conversion occurs post-translationally for the most part. We propose a model on the basis of these findings for the biogenesis of apo B.
Chuck
S L
SL
Department of Medicine, University of California 94143.
Yao
Z
Z
Blackhart
B D
BD
McCarthy
B J
BJ
Lingappa
V R
VR
D000818:Animals; D001055:Apolipoproteins B / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D002474:Cell-Free System; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006031:Glycosylation; D007700:Kinetics; D008861:Microsomes / Q000378:metabolism; D008970:Molecular Weight; D010179:Pancreas / Q000378:metabolism; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D012270:Ribosomes / Q000378:metabolism
D001055:Apolipoproteins B; C065032:apolipoprotein B-15