Structure of the Helicobacter pylori Cag type IV secretion system

Chung, Jeong Min; Sheedlo, M.J.; Campbell, Anne M.; Sawhney, Neha; Frick-Cheng, Arwen E; Lacy, D. Borden; Cover, Timothy L.; Ohi, Melanie D.

doi:10.7554/elife.47644

Cited by 87 publications

(170 citation statements)

References 29 publications

(75 reference statements)

Supporting

Mentioning

166

Contrasting

Order By: Relevance

“…CagY (residues 1677-1909) are localized to central regions of the O-layer of the OMC (Chung et al, 2019). The increased resolution of the new maps allowed us to define the OMC asymmetric unit and determine the molecular composition of regions that were previously undefined ( .…”

Section: Resultsmentioning

confidence: 99%

Cryo-EM reveals species-specific components within the Helicobacter pylori Cag type IV secretion system core complex

Sheedlo

Chung

Sawhney

et al. 2020

eLife

Self Cite

View full text Add to dashboard Cite

The pathogenesis of Helicobacter pylori-associated gastric cancer is dependent on delivery of CagA into host cells through a type IV secretion system (T4SS). The H. pylori Cag T4SS includes a large membrane-spanning core complex containing 5 proteins, organized into an outer membrane cap (OMC), a periplasmic ring (PR) and a stalk. Here, we report cryo-EM reconstructions of a core complex lacking Cag3 and an improved map of the wild-type complex. We define the structures of two unique species-specific components (Cag3 and CagM) and show that Cag3 is structurally similar to CagT. Unexpectedly, components of the OMC are organized in a 1:1:2:2:5 molar ratio (CagY:CagX:CagT:CagM:Cag3). CagX and CagY are components of both the OMC and the PR and bridge the symmetry mismatch between these regions. These results reveal that assembly of the H. pylori T4SS core complex is dependent on incorporation of interwoven species-specific components.

show abstract

Section: Resultsmentioning

confidence: 99%

Cryo-EM reveals species-specific components within the Helicobacter pylori Cag type IV secretion system core complex

Sheedlo

Chung

Sawhney

et al. 2020

eLife

Self Cite

View full text Add to dashboard Cite

show abstract

“…Structural details for several IVA machines have furthered our understanding of how these systems function. Xanthomonas citri VirB/D-, Helicobacter pylori Cag-, and E. coli R388-encoded IVA secretion machine structures resolved by single-particle cryoelectron microscopy (cryo-EM) and X-ray crystallography revealed that the IVA secretion machines are composed of an outer membrane-associated core complex (OMCC) that includes a large periplasmic assembly of proteins that connects to the secretion channel in the outer membrane (9)(10)(11)(12)(13). The OMCC recruits integral inner membrane (IM) proteins that connect to a cytoplasmic complex.…”

mentioning

confidence: 99%

Analysis of Dot/Icm Type IVB Secretion System Subassemblies by Cryoelectron Tomography Reveals Conformational Changes Induced by DotB Binding

Park

Chetrit

et al. 2020

mBio

View full text Add to dashboard Cite

Type IV secretion systems (T4SSs) are sophisticated nanomachines used by many bacterial pathogens to translocate protein and DNA substrates across a host cell membrane. Although T4SSs have important roles in promoting bacterial infections, little is known about the biogenesis of the apparatus and the mechanism of substrate transfer. Here, high-throughput cryoelectron tomography (cryo-ET) was used to visualize Legionella pneumophila T4SSs (also known as Dot/Icm secretion machines) in both the whole-cell context and at the cell pole. These data revealed the distribution patterns of individual Dot/Icm machines in the bacterial cell and identified five distinct subassembled intermediates. High-resolution in situ structures of the Dot/Icm machine derived from subtomogram averaging revealed that docking of the cytoplasmic DotB (VirB11-related) ATPase complex onto the DotO (VirB4-related) ATPase complex promotes a conformational change in the secretion system that results in the opening of a channel in the bacterial inner membrane. A model is presented for how the Dot/Icm apparatus is assembled and for how this machine may initiate the transport of cytoplasmic substrates across the inner membrane. IMPORTANCE Many bacteria use type IV secretion systems (T4SSs) to translocate proteins and nucleic acids into target cells, which promotes DNA transfer and host infection. The Dot/Icm T4SS in Legionella pneumophila is a multiprotein nanomachine that is known to translocate over 300 different protein effectors into eukaryotic host cells. Here, advanced cryoelectron tomography and subtomogram analysis were used to visualize the Dot/Icm machine assembly and distribution in a single L. pneumophila cell. Extensive classification and averaging revealed five distinct intermediates of the Dot/Icm machine at high resolution. Comparative analysis of the Dot/Icm machine and subassemblies derived from wild-type cells and several mutants provided a structural basis for understanding mechanisms that underlie the assembly and activation of the Dot/Icm machine.

show abstract

“…The apparent stoichiometric mismatches among subcomplexes could be in fact an important flexibility factor key to T4SS function. In this respect, it is interesting to note that the recently reported near‐atomic resolution structure of the Cag T4SS (Chung et al, ) shows that the 14‐fold symmetric outer membrane core complex connects to a newly described 17‐fold symmetric periplasmic ring complex. This new structure illustrates the structural diversity among T4SS.…”

Section: Structure and Function Of T3 T4 And T6ssmentioning

confidence: 96%

Bacterial injection machines: Evolutionary diverse but functionally convergent

Bleves

Galán

Llosa

2020

Cellular Microbiology

View full text Add to dashboard Cite

Many human pathogens use Type III, Type IV, and Type VI secretion systems to deliver effectors into their target cells. The contribution of these secretion systems to microbial virulence was the main focus of a workshop organised by the International University of Andalusia in Spain. The meeting addressed structure–function, substrate recruitment, and translocation processes, which differ widely on the different secretion machineries, as well as the nature of the translocated effectors and their roles in subverting the host cell. An excellent panel of worldwide speakers presented the state of the art of the field, highlighting the involvement of bacterial secretion in human disease and discussing mechanistic aspects of bacterial pathogenicity, which can provide the bases for the development of novel antivirulence strategies.

show abstract

Structure of the Helicobacter pylori Cag type IV secretion system

Cited by 87 publications

References 29 publications

Cryo-EM reveals species-specific components within the Helicobacter pylori Cag type IV secretion system core complex

Cryo-EM reveals species-specific components within the Helicobacter pylori Cag type IV secretion system core complex

Analysis of Dot/Icm Type IVB Secretion System Subassemblies by Cryoelectron Tomography Reveals Conformational Changes Induced by DotB Binding

Bacterial injection machines: Evolutionary diverse but functionally convergent

Contact Info

Product

Resources

About