6eup

Structural highlights

Function

NADA3_NEIMI Adheres to and induces bacterial uptake by human epithelial cells in a microfilament-dependent process. Binding is reduced by pronase treatment, suggesting there is a protein receptor on the human cells (PubMed:15660996, PubMed:30327444). Possible human protein receptors include integrin beta-1 (ITGB1) and oxidized low-density lipoprotein receptor 1 (OLR1) (Probable). Binds to extracellular human Hsp90 (preferentially the beta isoform, HSP90AB1) on monocytes, binding stimulates monocytes in a TLR4-dependent fashion, polymixin B, which binds NadA, blocks the activation. Hsp90 is probably not the first receptor on human monocytes (PubMed:21949862). Non-membrane anchored protein (residues 24-350) is internalized into human epithelial cells by hijacking the endosome recycling pathway and may be recycled back to the cell surface, which might aid transcellular trafficking of the bacteria (PubMed:25347845). A bacterial cell surface protein; antisera against this protein induce complement-mediated killing of this and other strains (PubMed:12045242).^{[1] [2] [3] [4] [5] [6]}

See Also

• Adhesin 3D structures

References

1. ↑ Comanducci M, Bambini S, Brunelli B, Adu-Bobie J, Aricò B, Capecchi B, Giuliani MM, Masignani V, Santini L, Savino S, Granoff DM, Caugant DA, Pizza M, Rappuoli R, Mora M. NadA, a novel vaccine candidate of Neisseria meningitidis. J Exp Med. 2002 Jun 3;195(11):1445-54. PMID:12045242 doi:10.1084/jem.20020407
2. ↑ Capecchi B, Adu-Bobie J, Di Marcello F, Ciucchi L, Masignani V, Taddei A, Rappuoli R, Pizza M, Aricò B. Neisseria meningitidis NadA is a new invasin which promotes bacterial adhesion to and penetration into human epithelial cells. Mol Microbiol. 2005 Feb;55(3):687-98. PMID:15660996 doi:10.1111/j.1365-2958.2004.04423.x
3. ↑ Cecchini P, Tavano R, Polverino de Laureto P, Franzoso S, Mazzon C, Montanari P, Papini E. The soluble recombinant Neisseria meningitidis adhesin NadA(Δ351-405) stimulates human monocytes by binding to extracellular Hsp90. PLoS One. 2011;6(9):e25089. PMID:21949862 doi:10.1371/journal.pone.0025089
4. ↑ Bozza G, Capitani M, Montanari P, Benucci B, Biancucci M, Nardi-Dei V, Caproni E, Barrile R, Picciani B, Savino S, Aricò B, Rappuoli R, Pizza M, Luini A, Sallese M, Merola M. Role of ARF6, Rab11 and external Hsp90 in the trafficking and recycling of recombinant-soluble Neisseria meningitidis adhesin A (rNadA) in human epithelial cells. PLoS One. 2014 Oct 27;9(10):e110047. PMID:25347845 doi:10.1371/journal.pone.0110047
5. ↑ Liguori A, Dello Iacono L, Maruggi G, Benucci B, Merola M, Lo Surdo P, Lopez-Sagaseta J, Pizza M, Malito E, Bottomley MJ. NadA3 Structures Reveal Undecad Coiled Coils and LOX1 Binding Regions Competed by Meningococcus B Vaccine-Elicited Human Antibodies. MBio. 2018 Oct 16;9(5). pii: mBio.01914-18. doi: 10.1128/mBio.01914-18. PMID:30327444 doi:http://dx.doi.org/10.1128/mBio.01914-18
6. ↑ Scietti L, Sampieri K, Pinzuti I, Bartolini E, Benucci B, Liguori A, Haag AF, Lo Surdo P, Pansegrau W, Nardi-Dei V, Santini L, Arora S, Leber X, Rindi S, Savino S, Costantino P, Maione D, Merola M, Speziale P, Bottomley MJ, Bagnoli F, Masignani V, Pizza M, Scharenberg M, Schlaeppi JM, Nissum M, Liberatori S. Exploring host-pathogen interactions through genome wide protein microarray analysis. Sci Rep. 2016 Jun 15;6:27996. PMID:27302108 doi:10.1038/srep27996
7. ↑ Liguori A, Dello Iacono L, Maruggi G, Benucci B, Merola M, Lo Surdo P, Lopez-Sagaseta J, Pizza M, Malito E, Bottomley MJ. NadA3 Structures Reveal Undecad Coiled Coils and LOX1 Binding Regions Competed by Meningococcus B Vaccine-Elicited Human Antibodies. MBio. 2018 Oct 16;9(5). pii: mBio.01914-18. doi: 10.1128/mBio.01914-18. PMID:30327444 doi:http://dx.doi.org/10.1128/mBio.01914-18