Separable ATPase and Membrane Insertion Domains of the SecA Subunit of Preprotein Translocase

Price, Albert; Economou, Anastassios; Duong, Franck; Wickner, William

doi:10.1074/jbc.271.49.31580

Cited by 64 publications

(120 citation statements)

References 31 publications

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“…Early work by several laboratories including our own showed that disruption or removal of the C-terminal domain of SecA led to elevation of its ATPase activity to levels near to those associated with translocation, increased signal sequence binding, and dissociation of the other domains. 72,74,75,88 In parallel, this C-terminal region was shown to be the region inserted into the membrane as SecA became a membrane-resident protein. 75,76,79,80 Thus, the picture that emerges is that the ligand-mediated triggering of domain dissociation leads to insertion of SecA into the membrane and activation of its translocase function.…”

Section: Seca Is Central To the Bacterial Sec Pathwaymentioning

confidence: 99%

“…72,74,75,88 In parallel, this C-terminal region was shown to be the region inserted into the membrane as SecA became a membrane-resident protein. 75,76,79,80 Thus, the picture that emerges is that the ligand-mediated triggering of domain dissociation leads to insertion of SecA into the membrane and activation of its translocase function. Economou's group 69,89 pointed to a specific region near the C-terminus, residues 783-795, that serves as an intramolecular regulator of ATPase activity (IRA1), and proposed that ligands (or deletion) caused the release of this IRA inhibition.…”

Section: Seca Is Central To the Bacterial Sec Pathwaymentioning

confidence: 99%

“…Studies from a variety of groups over the past decade have revealed that SecA is a multidomain protein that can exist as a monomer or a dimer, and that its domain rearrangements can be triggered by binding to any of its several ligands. 67,[69][70][71][72][73][74][75][76][77][78][79][80][81] The key to the conformational rearrangements appears to be intramolecular interactions that stabilize a more tightly packed, ''closed'' form of the protein. Weakening these interactions relieves these intramolecular constraints, and the protein domains partially dissociate, creating a less tightly packed, ''open'' form of the protein.…”

Section: Seca Is Central To the Bacterial Sec Pathwaymentioning

confidence: 99%

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Use of synthetic signal sequences to explore the protein export machinery

Clérico¹,

Maki²,

Gierasch³

2008

Biopolymers

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The information for correct localization of newly synthesized proteins in both prokaryotes and eukaryotes resides in self‐contained, often transportable targeting sequences. Of these, signal sequences specify that a protein should be secreted from a cell or incorporated into the cytoplasmic membrane. A central puzzle is presented by the lack of primary structural homology among signal sequences, although they share common features in their sequences. Synthetic signal peptides have enabled a wide range of studies of how these “zipcodes” for protein secretion are decoded and used to target proteins to the protein machinery that facilitates their translocation across and integration into membranes. We review research on how the information in signal sequences enables their passenger proteins to be correctly and efficiently localized. Synthetic signal peptides have made possible binding and crosslinking studies to explore how selectivity is achieved in recognition by the signal sequence‐binding receptors, signal recognition particle, or SRP, which functions in all organisms, and SecA, which functions in prokaryotes and some organelles of prokaryotic origins. While progress has been made, the absence of atomic resolution structures for complexes of signal peptides and their receptors has definitely left many questions to be answered in the future. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 90: 307–319, 2008.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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Section: Seca Is Central To the Bacterial Sec Pathwaymentioning

confidence: 99%

Section: Seca Is Central To the Bacterial Sec Pathwaymentioning

confidence: 99%

Section: Seca Is Central To the Bacterial Sec Pathwaymentioning

confidence: 99%

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Use of synthetic signal sequences to explore the protein export machinery

Clérico¹,

Maki²,

Gierasch³

2008

Biopolymers

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“…In the presence of preprotein and ATE or with the nonhydrolysable ATP analogue AMP-PNP alone, SecYEG-bound SecA undergoes a conformational change yielding a stable 30kDa fragment after proteolysis [21,27,28]. This fragment corresponds to a carboxy-terminal region of SecA [29] and its formation is reversed upon hydrolysis of ATE whereas it is stabilized by SecD and SecF [21]. Disruption of the membrane destabilizes the 30kDa fragment and it has been suggested that this SecA domain is deeply membrane-integrated, exposing regions at the periplasmic membrane face [27].…”

Section: Topology and Membrane Insertion Of Seca Domainsmentioning

confidence: 99%

The Sec system

Driessen

Fekkes

Wolk

1998

Current Opinion in Microbiology

159

111

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The Sec system Driessen, A.J.M.; Fekkes, P.; van der Wolk, J.P.W. Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Proteins designated to be secreted by Escherichia coil are synthesized with an amino-terminal signal peptide and associate as nascent chains with the export-specific chaperone SecB. Translocation occurs at a multisubunit membrane-bound enzyme termed translocase, which consists of a peripheral preprotein-binding site and an ATPase domain termed SecA, a core heterotrimeric integral membrane protein complex with SecY, SecE and SecG as subunits, and an accessory integral membrane protein complex containing SecD and SecE Major new insights have been gained into the cascade of preprotein targeting events and the enzymatic mechanism of preprotein translocation. It has become clear that preproteins are translocated in a stepwise fashion involving large nucleotide-induced conformational changes of the molecular motor SecA that propels the translocation reaction. Addresses

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“…The SecA protomer can be divided into two domains: an N-terminal domain, from residues 1-610, and a C-terminal domain, from 610 to 901. 30 The N-terminal ATPase domain contains seven consensus DEAD helicase motifs, 31,32 including the Walker A and B motifs 33 that are critical for high af®nity nucleotide binding and hydrolysis, 34 and it also contains a preprotein cross-linking site. 35 The N-terminal domain is able to bind peptides corresponding to signal sequences, and this binding decreases the intrinsic ATPase activity of the domain.…”

Section: Introductionmentioning

confidence: 99%