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Structure of a three-dimensional domain-swapped dimer of the Helicobacter pylori type IV secretion system pilus protein CagL.

Barden S, Schomburg B, Conradi J, Backert S, Sewald N, Niemann HH
Acta Crystallogr D Biol Crystallogr 70 1391-400 (2014)
Cited: 25 times
EuropePMC logo PMID: 24816107

Abstract

A new crystal form of the Helicobacter pylori type IV secretion system (T4SS) pilus protein CagL is described here. In contrast to two previously reported monomeric structures, CagL forms a three-dimensional domain-swapped dimer. CagL dimers can arise during refolding from inclusion bodies or can form spontaneously from purified monomeric CagL in the crystallization conditions. Monomeric CagL forms a three-helix bundle, with which the N-terminal helix is only loosely associated. In the new crystal form, the N-terminal helix is missing. The domain swap is owing to exchange of the C-terminal helix between the two protomers of a dimer. A loop-to-helix transition results in a long helix of 108 amino acids comprising the penultimate and the last helix of the monomer. The RGD motif of dimeric CagL adopts an α-helical conformation. In contrast to the previously reported structures, the conserved and functionally important C-terminal hexapeptide is resolved. It extends beyond the three-helix bundle as an exposed helical appendage. This new crystal form contributes to the molecular understanding of CagL by highlighting rigid and flexible regions in the protein and by providing the first view of the C-terminus. Based on the structural features, a previously unrecognized homology between CagL and CagI is discussed.

Reviews - 4cii mentioned but not cited (1)

  1. The Helicobacter pylori Cag Type IV Secretion System. Cover TL, Lacy DB, Ohi MD. Trends Microbiol 28 682-695 (2020)

Articles - 4cii mentioned but not cited (13)



Articles citing this publication (11)

  1. Genes required for assembly of pili associated with the Helicobacter pylori cag type IV secretion system. Johnson EM, Gaddy JA, Voss BJ, Hennig EE, Cover TL. Infect Immun 82 3457-3470 (2014)
  2. Integrin but not CEACAM receptors are dispensable for Helicobacter pylori CagA translocation. Zhao Q, Busch B, Jiménez-Soto LF, Ishikawa-Ankerhold H, Massberg S, Terradot L, Fischer W, Haas R. PLoS Pathog 14 e1007359 (2018)
  3. The Helicobacter pylori adhesin protein HopQ exploits the dimer interface of human CEACAMs to facilitate translocation of the oncoprotein CagA. Bonsor DA, Zhao Q, Schmidinger B, Weiss E, Wang J, Deredge D, Beadenkopf R, Dow B, Fischer W, Beckett D, Wintrode PL, Haas R, Sundberg EJ. EMBO J 37 e98664 (2018)
  4. Genetic diversity and amino acid sequence polymorphism in Helicobacter pylori CagL hypervariable motif and its association with virulence markers and gastroduodenal diseases. Yadegar A, Mohabati Mobarez A, Zali MR. Cancer Med 8 1619-1632 (2019)
  5. Helicobacter pylori CagL Y58/E59 mutation turns-off type IV secretion-dependent delivery of CagA into host cells. Tegtmeyer N, Lind J, Schmid B, Backert S. PLoS One 9 e97782 (2014)
  6. Systematic site-directed mutagenesis of the Helicobacter pylori CagL protein of the Cag type IV secretion system identifies novel functional domains. Bönig T, Olbermann P, Bats SH, Fischer W, Josenhans C. Sci Rep 6 38101 (2016)
  7. Preservation of Helicobacter pylori CagA Translocation and Host Cell Proinflammatory Responses in the Face of CagL Hypervariability at Amino Acid Residues 58/59. Tafreshi M, Zwickel N, Gorrell RJ, Kwok T. PLoS One 10 e0133531 (2015)
  8. Type IV secretion of Helicobacter pylori CagA into oral epithelial cells is prevented by the absence of CEACAM receptor expression. Tegtmeyer N, Ghete TD, Schmitt V, Remmerbach T, Cortes MCC, Bondoc EM, Graf HL, Singer BB, Hirsch C, Backert S. Gut Pathog 12 25 (2020)
  9. CagL polymorphisms D58/K59 are predominant in Helicobacter pylori strains isolated from Mexican patients with chronic gastritis. Román-Román A, Martínez-Santos VI, Castañón-Sánchez CA, Albañil-Muñoz AJ, González-Mendoza P, Soto-Flores DG, Martínez-Carrillo DN, Fernández-Tilapa G. Gut Pathog 11 5 (2019)
  10. Conformational changes of loops highlight a potential binding site in Rhodococcus equi VapB. Geerds C, Haas A, Niemann HH. Acta Crystallogr F Struct Biol Commun 77 246-253 (2021)
  11. Designed Ankyrin Repeat Proteins provide insights into the structure and function of CagI and are potent inhibitors of CagA translocation by the Helicobacter pylori type IV secretion system. Blanc M, Lettl C, Guérin J, Vieille A, Furler S, Briand-Schumacher S, Dreier B, Bergé C, Plückthun A, Vadon-Le Goff S, Fronzes R, Rousselle P, Fischer W, Terradot L. PLoS Pathog 19 e1011368 (2023)


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