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Chapter 20 : The Injectisome, a Complex Nanomachine for Protein Injection into Mammalian Cells

Authors: Maria Lara-Tejero, Jorge E. Galán
Content Type: Monograph
Publication Year: 2019

Category: Bacterial Pathogenesis

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Abstract:

Type III protein secretion systems (T3SSs) are multiprotein nanomachines present in many Gram-negative bacteria with a close relationship with a eukaryotic host. The primary function of these machines is the delivery of bacterially encoded effector proteins into target eukaryotic cells ( ), to modulate a myriad of cell biological processes for the benefit of the bacteria that encode them ( ). T3SSs are widespread in nature, playing a central role in the pathogenic and symbiotic interactions between many bacteria and their hosts. Among the bacteria that encode T3SSs are many important human and plant pathogens. As the field has progressed, so has the amount of information available, precluding a comprehensive review of the literature. Therefore, here we focus on the structural and architectural aspects of the type III system. To reflect current knowledge, and to help the reader better understand the structural organization of this machine, we refer throughout to the complete type III secretion machine as the injectisome, and we describe in detail the different substructures that integrate it (i.e., the needle complex [NC], the export apparatus, and the sorting platform). Readers are referred to other reviews for more specific aspects of the structure and function of these secretion machines ( ).

Citation: Lara-Tejero M, Galán J. 2019. The Injectisome, a Complex Nanomachine for Protein Injection into Mammalian Cells, p 245-259. In Sandkvist M, Cascales E, Christie P (ed), Protein Secretion in Bacteria. ASM Press, Washington, DC. doi: 10.1128/ecosalplus.ESP-0039-2018
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The Injectisome, a Complex Nanomachine for Protein Injection into Mammalian Cells
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Citation: Lara-Tejero M, Galán J. 2019. The Injectisome, a Complex Nanomachine for Protein Injection into Mammalian Cells, p 245-259. In Sandkvist M, Cascales E, Christie P (ed), Protein Secretion in Bacteria. ASM Press, Washington, DC. doi: 10.1128/ecosalplus.ESP-0039-2018
/content/10.1128/9781683670285.chap20.fig20-1
Figure 1
Surface view of the 3D reconstruction of the single-particle cryo-EM map of the needle complex (NC) substructure with the atomic structures of the different NC components docked. OR1, outer ring 1; OR2, outer ring 2; IR1, inner ring 1; IR2, inner ring 2. Central section of an overall cryo-ET structure of the complete injectisome . Of note is the location of IR2 in the cytosolic side of the bacterial envelope. IM, inner membrane; OM, outer membrane. Molecular model of the organization of the injectisome , with available atomic structures fitted into the model. Figure adapted from reference , with permission.
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10.1128/9781683670285/fig20-1.gif
Image of Figure 1
Figure 1

Surface view of the 3D reconstruction of the single-particle cryo-EM map of the needle complex (NC) substructure with the atomic structures of the different NC components docked. OR1, outer ring 1; OR2, outer ring 2; IR1, inner ring 1; IR2, inner ring 2. Central section of an overall cryo-ET structure of the complete injectisome . Of note is the location of IR2 in the cytosolic side of the bacterial envelope. IM, inner membrane; OM, outer membrane. Molecular model of the organization of the injectisome , with available atomic structures fitted into the model. Figure adapted from reference , with permission.

Citation: Lara-Tejero M, Galán J. 2019. The Injectisome, a Complex Nanomachine for Protein Injection into Mammalian Cells, p 245-259. In Sandkvist M, Cascales E, Christie P (ed), Protein Secretion in Bacteria. ASM Press, Washington, DC. doi: 10.1128/ecosalplus.ESP-0039-2018
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Figure 2
SctRST form a stable complex in the inner membrane, to which SctU is recruited. This complex nucleates the assembly of the IRs integrated by SctJ and SctD, which results in the extraction or “pulling” of the inner membrane components from the bacterial plasma membrane. At the same time, the secretin is independently assembled into the OR and the two structures come together to form the NC base substructure to which SctV is subsequently recruited. Once the NC base is formed, the cytoplasmic sorting platform is recruited to the cytoplasmic side of the NC base and the system starts to function as a type III secretion machine dedicated to the delivery of early substrates, such as the inner rod (SctI) and needle (SctF) subunits, to complete the assembly of the entire injectisome.
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10.1128/9781683670285/fig20-2.gif
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Figure 2

SctRST form a stable complex in the inner membrane, to which SctU is recruited. This complex nucleates the assembly of the IRs integrated by SctJ and SctD, which results in the extraction or “pulling” of the inner membrane components from the bacterial plasma membrane. At the same time, the secretin is independently assembled into the OR and the two structures come together to form the NC base substructure to which SctV is subsequently recruited. Once the NC base is formed, the cytoplasmic sorting platform is recruited to the cytoplasmic side of the NC base and the system starts to function as a type III secretion machine dedicated to the delivery of early substrates, such as the inner rod (SctI) and needle (SctF) subunits, to complete the assembly of the entire injectisome.

Citation: Lara-Tejero M, Galán J. 2019. The Injectisome, a Complex Nanomachine for Protein Injection into Mammalian Cells, p 245-259. In Sandkvist M, Cascales E, Christie P (ed), Protein Secretion in Bacteria. ASM Press, Washington, DC. doi: 10.1128/ecosalplus.ESP-0039-2018
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Figure 3
Activation of the injectisome leads to secretion of the translocators, which are deployed on the eukaryotic plasma membrane to form the translocon, which remains in contact with the needle to form a direct conduit between the bacterial and host cell cytosol that serves a passageway for the effector proteins. Figure adapted from reference , with permission.
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10.1128/9781683670285/fig20-3.gif
Image of Figure 3
Figure 3

Activation of the injectisome leads to secretion of the translocators, which are deployed on the eukaryotic plasma membrane to form the translocon, which remains in contact with the needle to form a direct conduit between the bacterial and host cell cytosol that serves a passageway for the effector proteins. Figure adapted from reference , with permission.

Citation: Lara-Tejero M, Galán J. 2019. The Injectisome, a Complex Nanomachine for Protein Injection into Mammalian Cells, p 245-259. In Sandkvist M, Cascales E, Christie P (ed), Protein Secretion in Bacteria. ASM Press, Washington, DC. doi: 10.1128/ecosalplus.ESP-0039-2018
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Tables

The Injectisome, a Complex Nanomachine for Protein Injection into Mammalian Cells
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Citation: Lara-Tejero M, Galán J. 2019. The Injectisome, a Complex Nanomachine for Protein Injection into Mammalian Cells, p 245-259. In Sandkvist M, Cascales E, Christie P (ed), Protein Secretion in Bacteria. ASM Press, Washington, DC. doi: 10.1128/ecosalplus.ESP-0039-2018
/content/10.1128/9781683670285.chap20.tab20-1
Table 1
Principal components of most studied T3SSs
Generic image for table
Table 1

Principal components of most studied T3SSs

Citation: Lara-Tejero M, Galán J. 2019. The Injectisome, a Complex Nanomachine for Protein Injection into Mammalian Cells, p 245-259. In Sandkvist M, Cascales E, Christie P (ed), Protein Secretion in Bacteria. ASM Press, Washington, DC. doi: 10.1128/ecosalplus.ESP-0039-2018

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