5YPZ

Crystal structure of minor pilin CofB from CFA/III complexed with N-terminal peptide fragment of CofJ

Summary for 5YPZ

• Entry DOI: 10.2210/pdb5ypz/pdb
• Descriptor: CofB, CofJ (2 entities in total)
• Functional Keywords: colonization factor, type ivb pili, minor pilin, cfa/iii, cell adhesion
• Biological source: Escherichia coli; More
• Total number of polymer chains: 6
• Total formula weight: 168237.37

Authors

Oki, H.,Kawahara, K.,Maruno, T.,Imai, T.,Muroga, Y.,Fukakusa, S.,Iwashita, T.,Kobayashi, Y.,Matsuda, S.,Kodama, T.,Iida, T.,Yoshida, T.,Ohkubo, T.,Nakamura, S. (deposition date: 2017-11-04, release date: 2018-06-27, Last modification date: 2024-11-20)

Primary citation

Oki, H.,Kawahara, K.,Maruno, T.,Imai, T.,Muroga, Y.,Fukakusa, S.,Iwashita, T.,Kobayashi, Y.,Matsuda, S.,Kodama, T.,Iida, T.,Yoshida, T.,Ohkubo, T.,Nakamura, S.
Interplay of a secreted protein with type IVb pilus for efficient enterotoxigenicEscherichia colicolonization.
Proc. Natl. Acad. Sci. U.S.A., 115:7422-7427, 2018

PubMed Abstract: Initial attachment and subsequent colonization of the intestinal epithelium comprise critical events allowing enteric pathogens to survive and express their pathogenesis. In enterotoxigenic (ETEC), these are mediated by a long proteinaceous fiber termed type IVb pilus (T4bP). We have reported that the colonization factor antigen/III (CFA/III), an operon-encoded T4bP of ETEC, possesses a minor pilin, CofB, that carries an H-type lectin domain at its tip. Although CofB is critical for pilus assembly by forming a trimeric initiator complex, its importance for bacterial attachment remains undefined. Here, we show that T4bP is not sufficient for bacterial attachment, which also requires a secreted protein CofJ, encoded within the same CFA/III operon. The crystal structure of CofB complexed with a peptide encompassing the binding region of CofJ showed that CofJ interacts with CofB by anchoring its flexible N-terminal extension to be embedded deeply into the expected carbohydrate recognition site of the CofB H-type lectin domain. By combining this structure and physicochemical data in solution, we built a plausible model of the CofJ-CFA/III pilus complex, which suggested that CofJ acts as a molecular bridge by binding both T4bP and the host cell membrane. The Fab fragments of a polyclonal antibody against CofJ significantly inhibited bacterial attachment by preventing the adherence of secreted CofJ proteins. These findings signify the interplay between T4bP and a secreted protein for attaching to and colonizing the host cell surface, potentially constituting a therapeutic target against ETEC infection.

PubMed: 29941571
DOI: 10.1073/pnas.1805671115

Experimental method

X-RAY DIFFRACTION (3.521 Å)