Many bacteria export effector proteins fulfilling their function in membranes of a eukaryotic host. These effector membrane proteins appear to contain signals for two incompatible bacterial secretion pathways in the same protein: a specific export signal, as well as transmembrane segments that one would expect to mediate targeting to the bacterial inner membrane. Here, we show that the transmembrane segments of effector proteins of type III and type IV secretion systems indeed integrate in the membrane as required in the eukaryotic host, but that their hydrophobicity in most instances is just below the threshold required for mediating targeting to the bacterial inner membrane. Furthermore, we show that binding of type III secretion chaperones to both the effector's chaperone-binding domain and adjacent hydrophobic transmembrane segments also prevents erroneous targeting. These results highlight the evolution of a fine discrimination between targeting pathways that is critical for the virulence of many bacterial pathogens.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6110835 | PMC |
| http://dx.doi.org/10.1038/s41467-018-05969-w | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Grass carp reovirus VP4 manipulates TOLLIP to degrade STING for inhibition of IFN production.
J Virol
January 2025
Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei, China.
Unlabelled: Although fish possess an effective interferon (IFN) system to defend against viral infection, grass carp reovirus (GCRV) still causes epidemic hemorrhagic disease and tremendous economic loss in grass carp. Therefore, it is necessary to investigate the immune escape strategies employed by GCRV. In this study, we show that the structural protein VP4 of GCRV (encoded by the S6 segment) significantly restricts IFN expression by degrading stimulator of IFN genes (STING) through the autophagy-lysosome-dependent pathway.
View Article and Find Full Text PDFImpact of Proximal Tubule-Specific Deletion of Dipeptidyl Peptidase 4 on Blood Pressure, Renal Sodium Handling, and NHE3 Phosphorylation.
bioRxiv
December 2024
Laboratorio de Genética e Cardiologia Molecular, Faculdade de Medicina, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.
Dipeptidyl peptidase 4 (DPP4) is a transmembrane serine exopeptidase abundantly expressed in the kidneys, predominantly in the proximal tubule (PT); however, its non-enzymatic functions in this nephron segment remain poorly understood. While DPP4 physically associates with the Na/H exchanger isoform 3 (NHE3) and its inhibitors exert natriuretic effects, the DPP4 role in blood pressure (BP) regulation remains controversial. This study investigated the effects of PT-specific deletion ( ) and global deletion ( ) on systolic blood pressure (SBP), natriuresis, and NHE3 regulation under baseline and angiotensin II (Ang II)-stimulated conditions in both male and female mice.
View Article and Find Full Text PDFA propofol binding site in the voltage sensor domain mediates inhibition of HCN1 channel activity.
Sci Adv
January 2025
Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Article Synopsis
- HCN ion channels play a key role in cellular activity and pain perception, with propofol acting as an analgesic by inhibiting their function.
- Researchers used a propofol analog to pinpoint binding sites on the human HCN1 isoform, revealing a specific pocket formed by certain residues in the channel.
- Mutations in this binding pocket affect propofol's ability to modulate HCN1 currents, highlighting its specific binding mechanism and offering insights for developing targeted HCN channel modulators.
Deep learning enhanced transmembranous electromyography in the diagnosis of sleep apnea.
BMC Neurosci
December 2024
Powell Mansfield, Inc., San Diego, CA, USA.
Obstructive sleep apnea (OSA) is widespread, under-recognized, and under-treated, impacting the health and quality of life for millions. The current gold standard for sleep apnea testing is based on the in-lab sleep study, which is costly, cumbersome, not readily available and represents a well-known roadblock to managing this huge societal burden. Assessment of neuromuscular function involved in the upper airway using electromyography (EMG) has shown potential to characterize and diagnose sleep apnea, while the development of transmembranous electromyography (tmEMG), a painless surface probe, has made this opportunity practical and highly feasible.
View Article and Find Full Text PDFPolar Networks Mediate Ion Conduction of the SARS-CoV-2 Envelope Protein.
J Am Chem Soc
January 2025
Department of Chemistry, Massachusetts Institute of Technology, 170 Albany Street, Cambridge, Massachusetts 02139, United States.
The SARS-CoV-2 E protein conducts cations across the cell membrane to cause pathogenicity to infected cells. The high-resolution structures of the E transmembrane domain (ETM) in the closed state at neutral pH and in the open state at acidic pH have been determined. However, the ion conduction mechanism remains elusive.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!