Regulation by the ribosome of the GTPase of the signal-recognition particle during protein targeting

Bacher, Gerald; Lütcke, Henrich; Jungnickel, Berit; Rapoport, Tom A.; Dobberstein, Bernhard

doi:10.1038/381248a0

Cited by 123 publications

(117 citation statements)

References 26 publications

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“…The latter result is consistent with the notion that several components of SRP are expected to interact with the ribosome, e.g. SRP54 as discussed in a previous section (Bacher et al, 1996). A direct interaction between the ribosome and the Alu-domain has recently also been confirmed by crosslinking experiments (M. Pool, B. Dobberstein, L. Terzi and K. Strub, unpublished results).…”

Section: Specific Contacts Between the Alu-domain And The Ribosome Efsupporting

confidence: 78%

“…An additional complexity is added to the topic by taking into consideration the as yet ill-defined role of ribosomes in signal sequence binding or recognition. Recently, a ribosomal component has been identified which stimulates GTP binding of SRP54 upon signal recognition (Bacher et al, 1996), indicating a direct interaction between SRP54 and ribosomal components.…”

Section: A Large Hydrophobic Groove Lined With Methionine Side Chainsmentioning

confidence: 99%

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New Insights into Signal Recognition and Elongation Arrest Activities of the Signal Recognition Particle

Bui

Strub²

1999

Biological Chemistry

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The signal recognition particle (SRP), a ubiquitous cytoplasmic ribonucleoprotein particle, plays an essential role in promoting co-translational translocation of proteins into the endoplasmic reticulum. Here, we summarise recent progress made in the understanding of two essential SRP functions: the signal recognition function, which ensures the specificity, and the elongation arrest function, which increases the efficiency of translocation. Our discussion is based on functional data as well as on atomic structure information, both of which also support the notion that SRP is a very ancient particle closely related to ribosomes. Based on the significant increase of knowledge that has been accumulating on the structure of elongation factors and on their interactions with the ribosome, we speculate about a possible mechanism of the elongation arrest function.

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Section: Specific Contacts Between the Alu-domain And The Ribosome Efsupporting

confidence: 78%

Section: A Large Hydrophobic Groove Lined With Methionine Side Chainsmentioning

confidence: 99%

New Insights into Signal Recognition and Elongation Arrest Activities of the Signal Recognition Particle

Bui

Strub²

1999

Biological Chemistry

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“…The SRP receptor itself consists of a 69-kDa α subunit and a 30-kDa β subunit and resides in the ER membrane. The SRP receptor (α and β) and the 54-kDa subunit of SRP are all GTPases that harness GTP to effect the docking of ribosomes and the transfer of signal sequences (Romisch et al, 1989) (Bacher et al, 1996) (Bacher et al, 1999). TRAM helps order the insertion process (Do et al, 1996) and determines the rate at which nascent chains are exposed to the lumen (Hegde et al, 1998c) as well as their topology (Hegde et al, 1998b).…”

Section: Protein Targeting To the Ermentioning

confidence: 99%

Glycoprotein Folding in the Endoplasmic Reticulum

Benham

Braakman

2000

Critical Reviews in Biochemistry and Molecular Biology

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Our understanding of eukaryotic protein folding in the endoplasmic reticulum has increased enormously over the last 5 years. In this review, we summarize some of the major research themes that have captivated researchers in this field during the last years of the 20th century. We follow the path of a typical protein as it emerges from the ribosome and enters the reticular environment. While many of these events are shared between different polypeptide chains, we highlight some of the numerous differences between proteins, between cell types, and between the chaperones utilized by different ER glycoproteins. Finally, we consider the likely advances in this field as the new century unfolds and we address the prospect of a unified understanding of how protein folding, degradation, and translation are coordinated within a cell.

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“…The ribosome may play an important role in signal sequence recognition by SRP54 since SRP fails to bind signal sequences of nascent chains that have been released from the ribosome (15,16). In addition, a ribosomal component stimulates GTP binding of SRP54 for an interaction with SR (17). Recently, two ribosomal proteins in proximity to the nascent chain exit site have been shown to interact in two distinct modes with SRP54 before and after binding to SR (18).…”

mentioning

confidence: 99%

Signal Recognition Particle Alu Domain Occupies a Defined Site at the Ribosomal Subunit Interface upon Signal Sequence Recognition

et al. 2003

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The eukaryotic signal recognition particle (SRP) is essential for cotranslational targeting of proteins to the endoplasmic reticulum (ER). The SRP Alu domain is specifically required for delaying nascent chain elongation upon signal sequence recognition by SRP and was therefore proposed to interact directly with ribosomes. Using protein cross-linking, we provide experimental evidence that the Alu binding protein SRP14 is in close physical proximity of several ribosomal proteins in functional complexes. Crosslinking occurs even in the absence of a signal sequence in the nascent chain demonstrating that SRP can bind to all translating ribosomes and that close contacts between the Alu domain and the ribosome are independent of elongation arrest activity. Without a signal sequence, SRP14 cross-links predominantly to a protein of the large subunit. Upon signal sequence recognition, certain cross-linked products become detectable or more abundant revealing a change in the Alu domain-ribosome interface. At this stage, the Alu domain of SRP is located at the ribosomal subunit interface since SRP14 can be cross-linked to proteins from the large and small ribosomal subunits. Hence, these studies reveal differential modes of SRP-ribosome interactions mediated by the Alu domain.Ribosomes translating mRNAs coding for secretory and membrane proteins are specifically targeted to the endoplasmic reticulum (ER) membrane by a cytosolic ribonucleoprotein particle, the signal recognition particle (SRP) (for review, see ref 1). The specificity of this process is ensured by the presence of a signal sequence in the growing peptide chain, which is recognized by SRP when it emerges from the ribosome. Signal sequence recognition by SRP causes a slow down or an arrest in the elongation of the nascent chain (2, 3). The SRP-ribosome-nascent chain complex is then targeted to the ER via the interaction of SRP with its membrane receptor, the SRP receptor (SR), a heterodimeric membrane protein (4,5). SR coordinates the release of SRP from the ribosome with the insertion of the nascent chain into the Sec61 complex, the aqueous translocation pore in the ER membrane (for reviews, see refs 6 and 7). Free SRP can then engage in another targeting round, and membraneassociated ribosomes resume translation at their regular speed, leading to the cotranslational transfer of the nascent chain across or into the ER membrane. As emphasized by

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Regulation by the ribosome of the GTPase of the signal-recognition particle during protein targeting

Cited by 123 publications

References 26 publications

New Insights into Signal Recognition and Elongation Arrest Activities of the Signal Recognition Particle

New Insights into Signal Recognition and Elongation Arrest Activities of the Signal Recognition Particle

Glycoprotein Folding in the Endoplasmic Reticulum

Signal Recognition Particle Alu Domain Occupies a Defined Site at the Ribosomal Subunit Interface upon Signal Sequence Recognition

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