Victoria Humbert, María Awanye, Amaka Marian Lian, Lu-Yun P. Derrick, Jeremy Christodoulides, Myron Structure of the <i>Neisseria</i> Adhesin Complex Protein (ACP) and its role as a novel lysozyme inhibitor <div><p>Pathogenic and commensal <i>Neisseria</i> species produce an Adhesin Complex Protein, which was first characterised in <i>Neisseria meningitidis</i> (Nm) as a novel surface-exposed adhesin with vaccine potential. In the current study, the crystal structure of a recombinant (r)Nm-ACP Type I protein was determined to 1.4 Å resolution: the fold resembles an eight-stranded β-barrel, stabilized by a disulphide bond between the first (Cys38) and last (Cys121) β-strands. There are few main-chain hydrogen bonds linking β4-β5 and β8-β1, so the structure divides into two four-stranded anti-parallel β-sheets (β1-β4 and β5-β8). The computed surface electrostatic charge distribution showed that the β1-β4 sheet face is predominantly basic, whereas the β5-β8 sheet is apolar, apart from the loop between β4 and β5. Concentrations of rNm-ACP and r<i>Neisseria gonorrhoeae</i>-ACP proteins ≥0.25 μg/ml significantly inhibited by ~80–100% (P<0.05) the <i>in vitro</i> activity of human lysozyme (HL) over 24 h. Specificity was demonstrated by the ability of murine anti-<i>Neisseria</i> ACP sera to block ACP inhibition and restore HL activity. ACP expression conferred tolerance to HL activity, as demonstrated by significant 3–9 fold reductions (P<0.05) in the growth of meningococcal and gonococcal <i>acp</i> gene knock-out mutants in the presence of lysozyme. In addition, wild-type <i>Neisseria lactamica</i> treated with purified ACP-specific rabbit IgG antibodies showed similar fold reductions in bacterial growth, compared with untreated bacteria (P<0.05). Nm-ACPI is structurally similar to the MliC/PliC protein family of lysozyme inhibitors. However, <i>Neisseria</i> ACP proteins show <20% primary sequence similarity with these inhibitors and do not share any conserved MliC/PliC sequence motifs associated with lysozyme recognition. These observations suggest that <i>Neisseria</i> ACP adopts a different mode of lysozyme inhibition and that the ability of ACP to inhibit lysozyme activity could be important for host colonization by both pathogenic and commensal <i>Neisseria</i> organisms. Thus, ACP represents a dual target for developing <i>Neisseria</i> vaccines and drugs to inhibit host-pathogen interactions.</p></div> wild-type Neisseria lactamica;main-chain hydrogen bonds;commensal Neisseria species;β1-β4 sheet face;novel lysozyme inhibitor Pathogenic;novel surface-exposed adhesin;block ACP inhibition;ACP-specific rabbit IgG antibodies;gonococcal acp gene;HL activity;Neisseria ACP sera;Adhesin Complex Protein;Neisseria Adhesin Complex Protein;protein;eight-stranded β- barrel;r Neisseria gonorrhoeae;1.4 Å resolution;commensal Neisseria organisms 2017-06-29
    https://plos.figshare.com/articles/dataset/Structure_of_the_i_Neisseria_i_Adhesin_Complex_Protein_ACP_and_its_role_as_a_novel_lysozyme_inhibitor/5160226
10.1371/journal.ppat.1006448