The SecA motor generates mechanical force during protein translocation

Gupta, Riti; Toptygin, Dmitri; Kaiser, Christian

doi:10.1038/s41467-020-17561-2

Cited by 31 publications

(20 citation statements)

References 64 publications

(112 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently published data support the fourth model, named the "Power-Stroke" (Catipovic et al, 2019;Catipovic, 2020;Gupta et al, 2020). According to this model, during translocation process IRA1 undergoes serious conformational changes caused by ATP binding and hydrolysis.…”

Section: Seca-dependent Protein Translocationmentioning

confidence: 94%

“…This clamp tightens around the substrate polypeptide while IRA1 is in a "resetting" state, and therefore the polypeptide cannot move forward. After ATP hydrolysis and release of inorganic phosphate (Pi), the clamp relaxes and the polypeptide passively slides through the SecY channel (Catipovic et al, 2019;Catipovic, 2020;Gupta et al, 2020).…”

Section: Seca-dependent Protein Translocationmentioning

confidence: 99%

See 1 more Smart Citation

SecA – a multidomain and multitask bacterial export protein

2021

View full text Add to dashboard Cite

Most bacterial secretory proteins destined to the extracytoplasmic space are secreted posttranslationally by the Sec translocase. SecA, a key component of the Sec system, is the ATPase motor protein, directly responsible for transferring the preprotein across the cytoplasmic membrane. SecA is a large protein, composed of several domains, capable of binding client preproteins and a variety of partners, including the SecYEG inner membrane channel complex, membrane phospholipids and ribosomes. SecA-mediated translocation can be divided into two major steps: (1) targeting of the preproteins to the membrane translocation apparatus and (2) transport across the membrane through the SecYEG channel. In this review we present current knowledge regarding SecA structure and function of this protein in both translocation steps. The most recent model of the SecA-dependent preprotein mechanical translocation across the bacterial cytoplasmic membrane is described. A possibility of targeting SecA with inhibitory compounds as a strategy to combat pathogenic bacteria will be discussed as well.

show abstract

Section: Seca-dependent Protein Translocationmentioning

confidence: 94%

Section: Seca-dependent Protein Translocationmentioning

confidence: 99%

SecA – a multidomain and multitask bacterial export protein

2021

View full text Add to dashboard Cite

show abstract

“…The SecY, SecE and SecG proteins together form the translocon complex SecYEG, an hourglass-shaped pore in the cell membrane with a constricted ring in the center 8 . Another component often described as the ‘motor’ that drives translocation is the ATPase SecA 9 . SecA can interact with both the pre-protein to be secreted and SecYEG 10 as it catalyzes the translocation of the polypeptide chain through ATP binding and hydrolysis 1 .…”

Section: Introductionmentioning

confidence: 99%

Protein secretion zones within the Gram-positive cell wall

Strach

Koch

Fiedler

et al. 2022

Preprint

View full text Add to dashboard Cite

Whereas the translocation of proteins across the cell membrane has been thoroughly investigated, it is still unclear how proteins cross the cell wall in Gram positive bacteria, which are widely used for industrial applications. We have studied secretion of α-amylase AmyE within two different Bacillus strains. We show that a C-terminal fusion of AmyE with the fluorescent reporter mCherry is secreted via discrete patches with very low dynamics that are visible at many places within the lateral cell wall, for many minutes. Expression from a high copy number plasmid was required to be able to see these structures we term "secretion zones". Zones corresponded to visualized AmyE activity on the surface of cells, and frequently overlapped with SecA signals, but did not necessarily co-localize with the secretion ATPase. Single particle tracking showed much higher dynamics of SecA and of SecDF, involved in AmyE secretion, at the cell membrane than AmyE. These experiments suggest that SecA initially translocates AmyE molecules through the cell membrane, and then diffuses to a different translocon. Single molecule tracking of SecA show changes in distinct diffusion states of SecA, but suggest that AmyE overexpression does not overwhelm the system. Because secretion zones were only found during the transition to and within stationary phase, diffusion rather than passive transport based on cell wall growth from inside to outside, releases AmyE and thus probably secreted proteins in general. Our findings suggest active transport through the cell membrane and slow, passive transition through the cell wall in Gram positive bacteria.

show abstract

“…SecA ATPase is one of the essential components in the Sec machinery, which provides a major pathway to help protein translocation from the cytosol across or into the cytoplasmic membrane. [5][6][7][8][9][10][11] Because SecA is a conserved and essential protein in all bacteria and is absent in humans, it is considered as a promising antibacterial drug target. At present, small organic molecules that can inhibit SecA mainly include Rose Bengal, [12] bisthiouracil, [13] bistriazole [14] and their derivatives, [15] thiazolo [4,5-d]pyrimidine derivatives [16] and others.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and biological evaluation of pyrimidine analogs as SecA inhibitors

et al. 2021

View full text Add to dashboard Cite

SecA, a key component of the bacterial Sec-dependent secretion pathway, is an attractive target for the development of new antimicrobial agents. We have previously reported pyrimidine analogs as SecA inhibitors.Herein, we report an extension of the earlier work in the synthesis and evaluation of a series of 15 5cyanothiouracil derivatives as SecA inhibitors. All the compounds have been evaluated for their inhibition of SecA ATPase (EcSecAN68) and for their antimicrobial activity against Escherichia coli NR698 (a leaky mutant) and Bacillus anthracis Sterne. Twelve compounds showed IC 50 of less than 6.3 µM when tested against EcSecAN68. In antimicrobial studies against E. coli NR698, six compounds showed MIC of less than 12.5 µM with three being less than 6.3 µM. Against B. anthracis Sterne, three compounds showed MIC of less than 6.3 µM.

show abstract

The SecA motor generates mechanical force during protein translocation

Cited by 31 publications

References 64 publications

SecA – a multidomain and multitask bacterial export protein

SecA – a multidomain and multitask bacterial export protein

Protein secretion zones within the Gram-positive cell wall

Design, synthesis, and biological evaluation of pyrimidine analogs as SecA inhibitors

Contact Info

Product

Resources

About