The Helicobacter pylori cag pathogenicity island as a determinant of gastric cancer risk

Figures & data

Figure 1. Organization of genes within the cag PAI. Five genes encoding proteins localized to the T4SS OMCC^10,11 and three genes encoding putative ATPases localized to the T4SS IMC are indicated. Genes required for Cag T4SS activity that lack homologs in other bacterial species are indicated with diagonal stripes.

Figure 2. Cag T4SS-mediated delivery of CagA and non-protein substrates into host cells. The Cag T4SS is required for delivery of CagA, LPS metabolites, peptidoglycan and DNA into host cells. Each substrate elicits a cellular response. CagA is phosphorylated by tyrosine kinases (such as Src), and phosphorylated CagA can cause disruptions to a variety of signaling pathways. LPS metabolites and peptidoglycan elicit NF-κB activation, leading to IL-8 production. DNA translocation causes TLR9 activation. Created with BioRender.com.

Figure 3. Structural organization of the Cag T4SS OMCC. The 14-fold-symmetric OMC and 17-fold-symmetric PR are illustrated.^10,11 (a, b, c) conserved Cag T4SS components. Purple = CagY, yellow = CagX, pink = CagT. (d, e, f) H. pylori-specific T4SS components. Blue = Cag3, green = CagM.

Table 1. cag PAI-encoded proteins that contribute to Cag T4SS activity.

Protein name	Synonym	Homologs	Molecular mass (kDa)	Localization or predicted localization ^a	Putative function
CagY	Cag7	VirB10	219	OMCC
CagX	Cag8	VirB9	61	OMCC
CagT	Cag12	VirB7	32	OMCC
Cagα		VirB11	37	IMC	ATPase
Cagβ	Cag5	VirD4	86	IMC	ATPase
CagE	Cag23	VirB3/VirB4	112	IMC	ATPase
CagC	Cag25	VirB2	12	IM, OM, S
CagV	Cag10	VirB8	29	IM
Cag4		VirB1	20	PP	PG hydrolase
CagA	Cag26		132	C, S	Effector protein
CagD	Cag24		24	IM, PP, S
CagF	Cag22		32	IM, C	CagA chaperone
CagG	Cag21		16	PP
CagH	Cag20		39	IM
CagI	Cag19		42	PP
CagL	Cag18		27	PP, S
CagN	Cag17		35	PP, IM
CagM	Cag16		44	OMCC
CagU	Cag11		25	IM
CagW	Cag9	VirB6	58	IM
CagZ	Cag6		23	IM
Cag3			55	OMCC

^aProtein localizations are based on subcellular fractionation analysis, cryo-ET analysis of the T4SS in intact bacteria, or single particle cryo-EM analysis of isolated complexes. Predicted localizations are based on based on protein sequence analysis or fractionation experiments. OM, outer membrane; IM, inner membrane; C, cytoplasm; S, surface-exposed or supernatant; PP, periplasm.

Chung JM, Sheedlo MJ, Campbell AM, Sawhney N, Frick-Cheng AE, Lacy DB, Cover TL, Ohi MD. Structure of the Helicobacter pylori Cag type IV secretion system. eLife. 2019;8:e47644. doi:10.7554/eLife.47644.

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Sheedlo MJ, Chung JM, Sawhney N, Durie CL, Cover TL, Ohi MD, Lacy DB. Cryo-EM reveals species-specific components within the Helicobacter pylori Cag type IV secretion system core complex. Elife. 2020;9:e59495. doi:10.7554/eLife.59495.

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