Abstract
Bacterial type IV secretion systems (T4SSs) are molecular machines that can mediate interbacterial DNA transfer through conjugation and delivery of effector molecules into host cells. The Helicobacter pylori Cag T4SS translocates CagA, a bacterial oncoprotein, into gastric cells, contributing to gastric cancer pathogenesis. We report the structure of a membrane-spanning Cag T4SS assembly, which we describe as three sub-assemblies: a 14-fold symmetric outer membrane core complex (OMCC), 17-fold symmetric periplasmic ring complex (PRC), and central stalk. Features that differ markedly from those of prototypical T4SSs include an expanded OMCC and unexpected symmetry mismatch between the OMCC and PRC. This structure is one of the largest bacterial secretion system assemblies ever reported and illustrates the remarkable structural diversity that exists among bacterial T4SSs.
Highlights
Bacterial pathogens are a threat to global health and have evolved elaborate strategies to infect their hosts
T4SSs in Gram-negative bacteria contain a minimum of 12 components, organized into an outer membrane core complex (OMCC), an inner membrane complex (IMC), and in some species an extracellular pilus (Christie et al, 2014; Grohmann et al, 2018; Waksman, 2019)
Cag T4SS complexes were purified from H. pylori as described (Frick-Cheng et al, 2016) and visualized by single particle cryo-EM (Figure 1 and Figure 1—figure supplement 1A,B)
Summary
Bacterial pathogens are a threat to global health and have evolved elaborate strategies to infect their hosts. T4SSs are found in a wide range of bacterial species, including many species that cause human disease, such as Helicobacter pylori, Legionella pneumophila, Bordetella pertussis, Brucella, and Bartonella (Christie et al, 2014; Grohmann et al, 2018). T4SSs in several bacterial species, including Helicobacter pylori and Legionella pneumophila, contain additional components, which are not present in the minimized systems
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