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Glycosylation can influence topogenesis of membrane proteins and reveals dynamic reorientation of nascent polypeptides within the translocon
- Source :
- The Journal of Cell Biology
- Publication Year :
- 1999
- Publisher :
- Rockefeller University Press, 1999.
-
Abstract
- The topology of multispanning membrane proteins in the mammalian endoplasmic reticulum is thought to be dictated primarily by the first hydrophobic sequence. We analyzed the in vivo insertion of a series of chimeric model proteins containing two conflicting signal sequences, i.e., an NH2-terminal and an internal signal, each of which normally directs translocation of its COOH-terminal end. When the signals were separated by more than 60 residues, linear insertion with the second signal acting as a stop-transfer sequence was observed. With shorter spacers, an increasing fraction of proteins inserted with a translocated COOH terminus as dictated by the second signal. Whether this resulted from membrane targeting via the second signal was tested by measuring the targeting efficiency of NH2-terminal signals followed by polypeptides of different lengths. The results show that targeting is mediated predominantly by the first signal in a protein. Most importantly, we discovered that glycosylation within the spacer sequence affects protein orientation. This indicates that the nascent polypeptide can reorient within the translocation machinery, a process that is blocked by glycosylation. Thus, topogenesis of membrane proteins is a dynamic process in which topogenic information of closely spaced signal and transmembrane sequences is integrated.
- Subjects :
- Glycosylation
Molecular Sequence Data
medicine.disease_cause
Endoplasmic Reticulum
chemistry.chemical_compound
Protein targeting
medicine
Animals
signal recognition particle
Amino Acid Sequence
Integral membrane protein
Binding Sites
biology
Membrane transport protein
Endoplasmic reticulum
Membrane Proteins
Biological Transport
Cell Biology
Translocon
Transmembrane protein
Biochemistry
Membrane protein
chemistry
COS Cells
biology.protein
Biophysics
signal sequence
Original Article
integral membrane protein
Sequence Analysis
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- The Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....0060bf94576580962feb156c310564a6
- Full Text :
- https://doi.org/10.5451/unibas-ep2560