Human heat shock protein (Hsp) 90 interferes with Neisseria meningitidis adhesin A (NadA)-mediated adhesion and invasion

Montanari, P.; Bozza, Giuseppe; Capecchi, Barbara; Caproni, Elena; Barrile, Riccardo; Norais, Nathalie; Capitani, Mirco; Sallese, Michele; Cecchini, Paola; Ciucchi, Laura; Gao, Zhenai; Rappuoli, Rino; Pizza, Mariagrazia; Aricò, Beatrice; Merola, Marcello

doi:10.1111/j.1462-5822.2011.01722.x

Cited by 32 publications

(34 citation statements)

References 69 publications

(125 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cell surface expression of HSP90 has been implicated in cancer invasion (31), autoimmunity (32), bacteria adhesion (33), and LPS signaling (34). However, the mechanism by which cell surface HSP90 exerts its function in these biological processes remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Chaperone gp96-independent Inhibition of Endotoxin Response by Chaperone-based Peptide Inhibitors

Dole

Hong

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: gp96 is a master chaperone for TLRs. A gp96-derived peptide (PIER) inhibits the LPS response. The underlying mechanism is unclear. Results: PIER inhibits LPS binding and signaling independently of gp96. It targets HSP90 and has anticancer activity. Conclusion: PIERs inhibit LPS responsiveness and tumor growth in a gp96-independent manner. Significance: This study facilitates the development of HSP90-based inhibitors to treat inflammation and cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Chaperone gp96-independent Inhibition of Endotoxin Response by Chaperone-based Peptide Inhibitors

Dole

Hong

et al. 2012

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Recent studies have shown that NadA is involved in interaction with and stimulation of immune cells during infection (2)(3)(4) and in binding to the human chaperone Hsp90 (5,6). Its predicted molecular structure is very similar to the known virulence-associated factors Yersinia adhesin A (YadA) and UspA2 (7,8), which suggests that NadA is a member of the OCA (oligomeric coiled-coil adhesin) family (9).…”

mentioning

confidence: 99%

Neisseria Adhesin A Variation and Revised Nomenclature Scheme

Bambini¹,

Chiara²,

Muzzi³

et al. 2014

Clin. Vaccine Immunol.

Self Cite

View full text Add to dashboard Cite

c Neisseria adhesin A (NadA), involved in the adhesion and invasion of Neisseria meningitidis into host tissues, is one of the major components of Bexsero, a novel multicomponent vaccine licensed for protection against meningococcal serogroup B in Europe, Australia, and Canada. NadA has been identified in approximately 30% of clinical isolates and in a much lower proportion of carrier isolates. Three protein variants were originally identified in invasive meningococci and named NadA-1, NadA-2, and NadA-3, whereas most carrier isolates either lacked the gene or harbored a different variant, NadA-4. Further analysis of isolates belonging to the sequence type 213 (ST-213) clonal complex identified NadA-5, which was structurally similar to NadA-4, but more distantly related to NadA-1, -2, and -3. At the time of this writing, more than 89 distinct nadA allele sequences and 43 distinct peptides have been described. Here, we present a revised nomenclature system, taking into account the complete data set, which is compatible with previous classification schemes and is expandable. The main features of this new scheme include (i) the grouping of the previously named NadA-2 and NadA-3 variants into a single NadA-2/3 variant, (ii) the grouping of the previously assigned NadA-4 and NadA-5 variants into a single NadA-4/5 variant, (iii) the introduction of an additional variant (NadA-6), and (iv) the classification of the variants into two main groups, named groups I and II. To facilitate querying of the sequences and submission of new allele sequences, the nucleotide and amino acid sequences are available at http://pubmlst.org/neisseria/NadA/.

show abstract

“…This adhesive activity has been mapped, at least partially, to an N-terminal region extending to residue T132 (23,24). Recently, interactions of NadA3 with β-1 integrin (25) and with the heat shock protein Hsp90 (26) have been reported.…”

mentioning

confidence: 99%

Structure of the meningococcal vaccine antigen NadA and epitope mapping of a bactericidal antibody

Malito

Biancucci

Faleri

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

105

View full text Add to dashboard Cite

Serogroup B Neisseria meningitidis (MenB) is a major cause of severe sepsis and invasive meningococcal disease, which is associated with 5-15% mortality and devastating long-term sequelae. Neisserial adhesin A (NadA), a trimeric autotransporter adhesin (TAA) that acts in adhesion to and invasion of host epithelial cells, is one of the three antigens discovered by genome mining that are part of the MenB vaccine that recently was approved by the European Medicines Agency. Here we present the crystal structure of NadA variant 5 at 2 Å resolution and transmission electron microscopy data for NadA variant 3 that is present in the vaccine. The two variants show similar overall topology with a novel TAA fold predominantly composed of trimeric coiled-coils with three protruding wing-like structures that create an unusual N-terminal head domain. Detailed mapping of the binding site of a bactericidal antibody by hydrogen/deuterium exchange MS shows that a protective conformational epitope is located in the head of NadA. These results provide information that is important for elucidating the biological function and vaccine efficacy of NadA.meningitis | coiled coil | thermostability | hydrogen-deuterium exchange | trimeric autotransporter adhesin

show abstract

Human heat shock protein (Hsp) 90 interferes with Neisseria meningitidis adhesin A (NadA)-mediated adhesion and invasion

Cited by 32 publications

References 69 publications

Chaperone gp96-independent Inhibition of Endotoxin Response by Chaperone-based Peptide Inhibitors

Chaperone gp96-independent Inhibition of Endotoxin Response by Chaperone-based Peptide Inhibitors

Neisseria Adhesin A Variation and Revised Nomenclature Scheme

Structure of the meningococcal vaccine antigen NadA and epitope mapping of a bactericidal antibody

Contact Info

Product

Resources

About