Structure and function of a membrane component SecDF that enhances protein export
Open accessAbstract
Protein translocation across the bacterial membrane, mediated by the secretory translocon SecYEG and the SecA ATPase, is enhanced by proton motive force and membrane-integrated SecDF, which associates with SecYEG. The role of SecDF has remained unclear, although it is proposed to function in later stages of translocation as well as in membrane protein biogenesis. Here, we determined the crystal structure of Thermus thermophilus SecDF at 3.3 Å resolution, revealing a pseudo-symmetrical, 12-helix transmembrane domain belonging to the RND superfamily and two major periplasmic domains, P1 and P4. Higher-resolution analysis of the periplasmic domains suggested that P1, which binds an unfolded protein, undergoes functionally important conformational changes. In vitro analyses identified an ATP-independent step of protein translocation that requires both SecDF and proton motive force. Electrophysiological analyses revealed that SecDF conducts protons in a manner dependent on pH and the presence of an unfolded protein, with conserved Asp and Arg residues at the transmembrane interface between SecD and SecF playing essential roles in the movements of protons and preproteins. Therefore, we propose that SecDF functions as a membrane-integrated chaperone, powered by proton motive force, to achieve ATP-independent protein translocation.
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SecDF has been demonstrated to interact with the SecYEG translocon and enhance its translocation efficacy by proton-motive force transduced to SecYEG.
“SecDF has been demonstrated to interact with the SecYEG translocon, which comprises secY/0652, secE/0839, and secG/0774, and enhance its translocation efficacy by proton-motive force that is transduced to SecYEG.80”
From Toward the Complete Functional Characterization of a Minimal Bacterial Proteome (2022) · cites this paper as [80]
The Abstract says SecDF associates with SecYEG and that SecDF and proton-motive force enhance protein translocation. In the discussion of its proposed mechanism (indexed under Abstract; page unavailable), the paper describes proton flow driving conformational changes in SecDF, not proton-motive force being transduced to SecYEG. That specific mechanism is unsupported. (LLM, conf=0.87)
Experimental — accuracy not yet measuredGene /0412 is secDF, a protein translocase subunit involved in cell membrane.
“secDF/0412 | cell membrane | protein translocase subunit”
From Toward the Complete Functional Characterization of a Minimal Bacterial Proteome (2022) · cites this paper as [80]
The paper describes SecDF as a membrane-integrated component that assists protein translocation (Abstract; page unavailable). It does not identify a gene designated /0412 as secDF, so that specific gene assignment is not supported by our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredGene /0412 is a putative secDF protein export enhancing membrane component.
“we have further support to annotate /0412 as a putative secDF protein export enhancing membrane component.”
From Toward the Complete Functional Characterization of a Minimal Bacterial Proteome (2022) · cites this paper as [80]
For being active in protein transport, the SecYEG translocon depends on the coordinated interaction with multiple partner proteins that select potential SecYEG substrates, provide the driving force for protein transport, coordinate substrate release from the SecYEG channel, and communicate with components of the proteostasis network.
“For being active in protein transport, the SecYEG translocon depends on the coordinated interaction with multiple partner proteins that select potential SecYEG substrates (Lill et al., 1990; van der Does et al., 1996; Angelini et al., 2005), provide the driving force for protein transport (Tsukazaki et al., 2011; Knyazev et al., 2018), coordinate substrate release from the SecYEG channel (Beck et”
From The Dynamic SecYEG Translocon (2021) · cites this paper as Tsukazaki et al., 2011
The crystal structure of the SecDF complex shows 12 TMs, six each in SecD and SecF, and three periplasmic domains, termed P1-head, P1-base and P4.
“The crystal structure of the SecDF complex shows 12 TMs, six each in SecD and SecF, and three periplasmic domains, termed P1-head, P1-base and P4 (Tsukazaki et al., 2011; Figure 10B).”
From The Dynamic SecYEG Translocon (2021) · cites this paper as Tsukazaki et al., 2011
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- Authors
- Tsukazaki, T., Mori, H., Echizen, Y., Ishitani, R., Fukai, S., Tanaka, T., Perederina, A., Vassylyev, D. G., Kohno, T., Maturana, A. D., Ito, K., & Nureki, O.
- Affiliations
- The University of Tokyo (JP)
- Kyoto University (JP)
- Synchrotron Radiation Collaborative Research Organization, The University of Tokyo (JP)
- University of Alabama at Birmingham (US)
- Nagaoka University of Technology (JP)
- Kyoto Sangyo University (JP)
- Corresponding author
- Ito, Koreaki
- Nureki, Osamu
- ORCID
- Venue
- Nature
- Published
- 2011-05-11
- Volume
- 474
- Issue
- 7350
- Pages
- 235-238
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3697915
- OpenAlex
- W2132192325
- Cited by
- 219
- References
- 27
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 7 · 2023: 6 · 2022: 12 · 2021: 10 · 2020: 9 · 2019: 23 · 2018: 20 · 2017: 19 · 2016: 22 · 2015: 16 · 2014: 19 · 2013: 24 · 2012: 8
- FWCI
- 11.36
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (22370070, 22121003, 21770135, 23657128, 22687007, 22117007, 21687009, 20227003, 20247020)
- National Institute of General Medical Sciences (R01GM074840)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- SecDF, SecYEG translocon, protein translocation, bacterial protein secretion, proton motive force, RND superfamily, Thermus thermophilus, crystal structure, periplasmic domain, SecA ATPase, proton conduction, unfolded protein binding, membrane protein biogenesis
- MeSH terms
- Adenosine Triphosphate, Arginine, Asparagine, Bacterial Proteins, Hydrogen-Ion Concentration, Membrane Proteins, Models, Biological, Models, Molecular, Structure-Activity Relationship, Thermus thermophilus, Protein Structure, Tertiary, Crystallography, X-Ray, Proton-Motive Force, Periplasm, Nuclear Magnetic Resonance, Biomolecular, Protein Transport, Membrane Transport Proteins, Static Electricity, Protein Unfolding
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