Báo cáo khoa học: Structural and functional aspects of unique type IV secretory components in the

MINIREVIEW

Structural and functional aspects of unique type IV

secretory components in the Helicobacter pylori

cag-pathogenicity island

Laura Cendron1 and Giuseppe Zanotti2

1 Department of Biological Chemistry, University of Padua, Italy

2 Venetian Institute of Molecular Medicine (VIMM), Padua, Italy

Introduction

Cytotoxin-associated gene-pathogenicity island (cagPAI)

characterizes the type I strains of Helicobacter pylori

(i.e. the virulent strains) responsible for most gastroduo￾denal diseases, including active chronic gastritis, peptic

ulcers, gastric adenocarcinoma and mucosa-associated

lymphoid tissue lymphoma [1–3]. CagA, a major anti￾genic factor of the bacterium, is the main signature of

the cagPAI-positive strains. Indeed, cagPAI confers

H. pylori the capability to express and translocate the

CagA protein inside the host cell through a secretion

machinery, which is coded by the components of the

PAI; see the accompanying review by Fischer [4]. Once

translocated, CagA associates with the inner side of the

membrane and is phosphorylated at EPIYA motifs by

Keywords

3D structure; Cag proteins; gastric cancer;

Helicobacter pylori; type IV secretion

system

Correspondence

G. Zanotti, Department of Biological

Chemistry, University of Padua, Viale G.

Colombo 3, 35121 Padua, Italy

Fax: +39 0498073310

Tel: +39 0498276409

E-mail: [email protected]

(Received 16 November 2010, revised 10

January 2011, accepted 27 January 2011)

doi:10.1111/j.1742-4658.2011.08038.x

Helicobacter pylori cytotoxin-associated gene-pathogenicity island (cagPAI)

is responsible for the secretion of the CagA effector through a type IV

secretion system (T4SS) apparatus, as well as of peptidoglycan and possibly

other not yet identified factors. Twenty-nine different polypeptide chains

are encoded by this cluster of genes, although only some of them show a

significant similarity with the constitutive elements of well characterized

secretion systems from other bacteria. The other cagPAI components repre￾sent almost unique proteins in this scenario. The majority of the T4SS

include approximately fifteen components, taking into account either the

transmembrane complex subunits, ATPases or substrate factors. The com￾position of the cagPAI is very complex: it includes proteins most likely

involved at different levels in the pilus assembly, stabilization and process￾ing of secreted substrate, as well as regulatory particles possibly involved in

the control of the entire apparatus. Despite recent findings with respect to

components that play a role in the interaction with the host cell, the func￾tion of several cagPAI proteins remains unclear or unknown. This is partic￾ularly true for those that represent unique members with no clear similarity

to those of other T4SS and no obvious evidence of involvement in the

secretion of CagA or induction of pro-inflammatory responses. We summarize

what is known about these accessory components, both from a molecular

and structural point of view, as well as their putative physiological role.

Abbreviations

cagPAI, cytotoxin-associated gene-pathogenicity island; IL, interleukin; T4SS, type IV secretion system.

FEBS Journal 278 (2011) 1223–1231 ª 2011 The Authors Journal compilation ª 2011 FEBS 1223