Role of Ribosomes in Reinitiation of Membrane Insertion of Internal Transmembrane Segments in a Polytopic Membrane Protein

详细信息    查看全文

• 作者：Changsen Wang ; Mingang Chen ; Ernest Han ; and Jian-Ting Zhang
• 刊名：Biochemistry
• 出版年：1997
• 出版时间：September 23, 1997
• 年：1997
• 卷：36
• 期：38
• 页码：11437 - 11443
• 全文大小：258K
• 年卷期：v.36,no.38(September 23, 1997)
• ISSN：1520-4995

文摘

The topogenesis of membrane proteins with a single transmembrane(TM) segment is wellunderstood. However, understanding the topogenesis and membraneassembly of membrane proteinswith multiple TM segments (polytopic) is still incomplete.Recently, several studies on P-glycoprotein(Pgp) suggested that the topogenesis of polytopic membrane proteins islikely more complicated thananticipated. While studying the mechanism by which Pgp topogenesisis determined, we unexpectedlyfound that ribosomes or proteins associated with ribosomes are involvedin regulating the membraneinsertion and folding of Pgp during its translation. We discoveredthat when Pgp was translated by wheatgerm ribosomes in vitro, TM3 could not reinitiate theinsertion of the protein into microsomal membranesfollowing the membrane insertion of TM1 and TM2. In contrast, TM3could reinitiate membrane insertionwhen the protein was translated by rabbit reticulocyte ribosomes.These findings suggest that ribosomesor proteins associated with ribosomes play an important role inmembrane insertion and folding of TMsegments of Pgp and that rabbit reticulocyte and wheat germ ribosomesmay use different mechanisms tocontrol the membrane insertion of the same nascent peptide. Wepropose that ribosomes or proteinsassociated with ribosomes help reinitiate insertion of internal TMsegments into the membrane bydissociation and reassociation with the protein-conducting channel inER membranes.