Signal Sequence-Dependent Function of the TRAM Protein during Early Phases of Protein Transport across the Endoplasmic Reticulum Membrane

Cotranslational translocation of proteins across the mammalian ER membrane involves, in addition to the signal recognition particle receptor and the Sec61p complex, the translocating chain-associating membrane (TRAM) protein, the function of which is still poorly understood. Using reconstituted prot...

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Bibliographic Details
Published in:The Journal of cell biology 1996-07, Vol.134 (1), p.25-35
Main Authors: Voigt, Sabine, Jungnickel, Berit, Hartmann, Enno, Rapoport, Tom A.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amino acids
Animals
Biological Transport
Cell-Free System
Cellular biology
Dogs
Endoplasmic reticulum
Endoplasmic Reticulum, Rough - metabolism
Membrane Glycoproteins - metabolism
Membrane Proteins - metabolism
Membranes
Microsomes
Molecular Sequence Data
Open reading frames
P branes
Plasmids
Protein Sorting Signals - physiology
Protein transport
Proteins
Receptors
Receptors, Cytoplasmic and Nuclear - metabolism
Receptors, Peptide - metabolism
Ribosomes
SEC Translocation Channels
Solubility
Structure-Activity Relationship
Trolley cars
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Summary:Cotranslational translocation of proteins across the mammalian ER membrane involves, in addition to the signal recognition particle receptor and the Sec61p complex, the translocating chain-associating membrane (TRAM) protein, the function of which is still poorly understood. Using reconstituted proteoliposomes, we show here that the translocation of most, but not all, secretory proteins requires the function of TRAM. Experiments with hybrid proteins demonstrate that the structure of the signal sequence determines whether or not TRAM is needed. Features that distinguish TRAM-dependent and -independent signal sequences include the length of their charged, NH2-terminal region and the structure of their hydrophobic core. In cases where TRAM is required for translocation, it is not needed for the initial interaction of the ribosome/nascent chain complex with the ER membrane but for a subsequent step inside the membrane in which the nascent chain is inserted into the translocation site in a protease-resistant manner. Thus, TRAM functions in a signal sequence-dependent manner at a critical, early phase of the translocation process.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.134.1.25